Definition
Williams syndrome is a genetic disorder caused by a deletion of a series of genes on chromosome 7q11. Individuals with Williams syndrome have distinctive facial features, mild mental retardation, heart and blood vessel problems, short stature, unique personality traits, and distinct learning abilities and deficits.
Description
Williams syndrome, also known as Williams Beuren syndrome, was first described in 1961 by Dr. J.C.P. Williams of New Zealand. At that time it was noted that individuals with Williams syndrome had an unusual constellation of physical and mental findings. The physical features include a characteristic facial appearance, heart and cardiovascular problems, high blood calcium levels, low birth weight, short stature, and other connective tissue abnormalities. The intellectual problems associated with Williams include a mild mental retardation and a specific cognitive profile. That is, individuals with Williams syndrome often have the same pattern of learning abilities and disabilities, as well as many similar personality traits.
The findings in Williams syndrome are variable—that is, not all individuals with Williams syndrome will have all of the described findings. In addition to being variable, the physical and mental findings associated with Williams syndrome are progressive—they change over time.
Genetic profile
Williams syndrome is a genetic disorder due to a deletion of chromosome material on the long arm of chromosome 7. A series of genes are located in this region. Individuals with Williams syndrome may have some or all of these genes deleted. Because of this, Williams syndrome is referred to as a contiguous gene deletion syndrome. Contiguous refers to the fact that these genes are arranged next to each other. The size of the deletion can be large or small, which may explain why some individuals with Williams syndrome are more severely affected than others. If you think of these genes as the letters of the alphabet, some individuals with Williams syndrome are missing A to M, some are missing G to Q and others are missing A to R. While there are differences in the amount of genetic material that can be deleted, there is a region of overlap. Everyone in the above example was missing G to M. It is thought that the missing genes in this region are important causes of the physical and mental findings of Williams syndrome.
Two genes in particular, ELN and LIMK1, have been shown to be important in causing some of the characteristic symptoms of Williams syndrome. The ELN gene codes for a protein called elastin. The job of elastin in the human body is to provide elasticity to the connective tissues such as those in the arteries, joints, and tendons. The exact role of the LIMK1 gene is not known. The gene codes for a substance known as lim kinase 1 that is active in the brain. It is thought that the deletion of the LIMK1 gene may be responsible for the visuospatial learning difficulties of individuals with Williams syndrome. Many other genes are known to be in the deleted region of chromosome 7q11 responsible for Williams syndrome and much work is being done to determine the role of these genes in Williams syndrome.
Williams syndrome is an autosomal dominant disorder. Genes always come in pairs and in an autosomal dominant disorder, only one gene need be missing or altered for an individual to have the disorder. Although Williams syndrome is an autosomal disorder, most individuals with Williams syndrome are the only people in their family with this disorder. When this is the case, the chromosome deletion that causes Williams syndrome is called de novo. A de novo deletion is one that occurs for the first time in the affected individual. The cause of de novo chromosome deletions is unknown. Parents of an individual with Williams syndrome due to a de novo deletion are very unlikely to have a second child with William syndrome. However, once an individual has a chromosome deletion, there is a 50% chance that he or she will pass it on to their offspring. Thus individuals with Williams syndrome have a 50% chance of passing this deletion (and Williams syndrome) to their children.
Demographics
Williams syndrome occurs in 1 in 20,000 births. Because Williams syndrome is an autosomal dominant disorder, it affects an equal number of males and females. It is thought that Williams syndrome occurs in people of all ethnic backgrounds equally.
Signs and symptoms
Williams syndrome is a multi-system disorder. In addition to distinct facial features, individuals with Williams syndrome can have cardiovascular, growth, joint, and other physical problems. They also share unique personality traits and have intellectual differences.
Infants with Williams syndrome are often born small for their family and 70% are diagnosed with failure to thrive during infancy. These growth problems continue throughout the life of a person with Williams syndrome and most individuals with Williams syndrome have short stature (height below the third percentile). Infants with William syndrome can also be extremely irritable and have "colic-like" behavior. This behavior is thought to be due to excess calcium in the blood (hypercalcemia). Other problems that can occur in the first years include strabismus (crossed eyes), ear infections, chronic constipation, and eating problems.
Individuals with Williams syndrome can have distinct facial features sometimes described as "elfin" or "pixie-like." While none of these individual facial features are abnormal, the combination of the different features is common for Williams syndrome. Individuals with Williams syndrome have a small upturned nose, a small chin, long upper lip with a wide mouth, small widely spaced teeth, and puffiness around the eyes. As an individual gets older, these facial features become more pronounced.
People with Williams syndrome often have problems with narrowing of their heart and blood vessels. This is thought to be due to the deletion of the elastin gene and is called elastin arteriopathy. Any artery in the body can be affected, but the most common narrowing is seen in the aorta of the heart. This condition is called supravalvar aortic stenosis (SVAS) and occurs in approximately 75% of individuals with Williams syndrome. The degree of narrowing is variable. If left untreated, it can lead to high blood pressure, heart disease, and heart failure. The blood vessels that lead to the kidney and other organs can also be affected.
Deletions of the elastin gene are also thought to be responsible for the loose joints of some children with Williams syndrome. As individuals with Williams syndrome age, their heel cords and hamstrings tend to tighten, which can lead to a stiff awkward gait and curving of the spine.
Approximately 75% of individuals with Williams syndrome have mild mental retardation. They also have a unique cognitive profile (unique learning abilities and disabilities). This cognitive profile is independent of their IQ. Individuals with Williams syndrome generally have excellent language and memorization skills. They can have extensive vocabularies and may develop a thorough knowledge of a topic that they are interested in. Many individuals are also gifted musicians. Individuals with Williams syndrome have trouble with concepts that rely on visuospatial ability. Because of this, many people with Williams syndrome have trouble with math, writing and drawing.
People with Williams syndrome also often share personality characteristics. They are noted to be very talkative and friendly—sometimes inappropriately—and they can be hyperactive. Another shared personality trait is a generalized anxiety.
Diagnosis
The diagnosis of Williams syndrome is usually made by a physician familiar with Williams syndrome and based upon a physical examination of the individual and a review of his or her medical history. It is often made in infants after a heart problem (usually SVAS) is diagnosed. In children without significant heart problems, the diagnosis may be made after enrollment in school when they are noted to be "slow learners."
While a diagnosis can be made based upon physical examination and medical history, the diagnosis can now be confirmed by a DNA test.
Williams syndrome is caused by a deletion of genetic material from the long arm of chromosome 7. A specific technique called fluorescent in situ hybridization testing, or FISH testing, can determine whether there is genetic material missing. A FISH test will be positive (detect a deletion) in over 99% of individuals with Williams syndrome. A negative FISH test for Williams syndrome means that no genetic material is missing from the critical region on chromosome 7q11.
Prenatal testing (testing during pregnancy) for Williams syndrome is possible using the FISH test on DNA sample obtained by chorionic villus sampling (CVS) or by amniocentesis. Chorionic villus sampling is a prenatal test that is usually done between 10 and 12 weeks of pregnancy and involves removing a small amount of tissue from the placenta. Amniocentesis is a prenatal test that is usually performed at 16–18 weeks of pregnancy and involves removing a small amount of the amniotic fluid that surrounds the fetus. DNA is obtained from these samples and tested to see if the deletion responsible for Williams syndrome is present. While prenatal testing is possible, it is not routinely performed. Typically, the test is only done if there is a family history of Williams syndrome.
Treatment and management
Because Williams syndrome is a multi-system disorder, the expertise of a number of specialists is required for management of this disorder.
The height and growth of individuals with Williams syndrome should be monitored using special growth curves developed specifically for individuals with Williams syndrome. Individuals who fall off these growth curves should be worked up for possible eating or thyroid disorders
A cardiologist should evaluate individuals with Williams syndrome yearly. This examination should include measurement of blood pressure in all four limbs and an echocardiogram of the heart. An echocardiogram is a special form of ultrasound that looks at the structure of the heart. Doppler flow studies, which look at how the blood flows into and out of the heart, should also be done. Individuals with supravalvar stenosis may require surgery to fix this condition. The high blood pressure caused by this condition may be treated with medication. Examinations should take place yearly as some of these conditions are progressive and may worsen over time.
Individuals with Williams syndrome should also have a complete neurological examination. In addition, the blood calcium levels of individuals with Williams syndrome should be monitored every two years. High levels of calcium can cause irritability, vomiting, constipations and muscle cramps. An individual found to have a high level of calcium should consult a nutritionist to make sure that their intake of calcium is not higher than 100% of the recommended daily allowance (RDA). Because vitamin D can increase calcium levels, individuals with Williams syndrome and high calcium should not take multivitamins containing vitamin D. If calcium levels remain high after limiting vitamin D and decreasing dietary intake of calcium, an individual with hypercalcemia should see a nephrologist for further management and to monitor kidney function.
Strabismus (crossed eyes) can be treated by patching or by surgery. Ear infections can be treated with antibiotics and surgical placement of ear tubes.
The developmental differences of individuals with Williams syndrome should be treated with early intervention and special education classes. Specific learning strategies that capitalize on the strengths of individuals with Williams syndrome should be used. Physical, occupational, and speech therapy should be provided. Behavioral counseling and medication may help with behavioral problems such as hyperactivity and anxiety.
Prognosis
The prognosis for individuals with Williams syndrome is highly dependent on the medical complications of a particular individual.
Saturday, December 29, 2007
Definition
Sanfilippo syndrome is an inherited disease of metabolism that makes the body unable to properly break down long chains of sugar molecules called glycosaminoglycans (formerly called mucopolysaccharides).
The syndrome belongs to a group of diseases called mucopolysaccharidoses (MPS). Specifically, it is known as MPS III.
See also:
MPS I H (Hurler syndrome)
MPS II, Hunter syndrome
MPS IV (Morquio syndrome)
MPS I S (Scheie syndrome)
Alternative Names
MPS III
Causes, incidence, and risk factors
Sanfilippo syndrome occurs when the substances (enzymes) needed to break down the heparan sulfate sugar chain are missing or are defective.
There are four main types of Sanfilippo syndrome, also called MPS III. Which type a person has depends on which enzyme is affected.
Sanfilippo type A is the most severe form. Persons with this type are missing or have an altered form of an enzyme called heparan N-sulfatase.
Sanfilippo type B occurs when a person is missing or doesn't not produce enough alpha-N-acetylglucosaminidase.
Sanfilippo C occurs when a person is missing or doesn't not produce enough acetyl-CoAlpha-glucosaminide acetyltransferase.
Sanfilippo D occurs when a person is missing or doesn't not produce enough N-acetylglucosamine 6-sulfatase.
The syndrome is inherited as an autosomal recessive trait. That means both your parents must pass you the defective gene in order for you to get this disease.
Sanfilippo syndrome is possibly the most common forms of MPS. It is seen in about 1 in 70,000 births. A family history of Sanfilippo syndrome increases one's risk for this condition.
Symptoms
Unlike other forms of MPS, symptoms appear after the first year of life. A decline in learning ability typically occurs between ages 2 and 6. The child may have normal growth during first few years, but final height is below average. Delayed development is followed by deteriorating mental status.
Other symptoms include:
Walking problems
Coarse facial features
Full lips
Heavy eyebrows that meet in the middle of the face above the nose
Diarrhea
Stiff joints that may not extend fully
Signs and tests
A physical exam may show signs of liver and spleen swelling. An eye exam will show clear corneas, unlike the cloudy corneas seen in persons with Hurler syndrome (MPS I H). Neurological testing will reveal signs of seizures and mental retardation.
Urine tests will be done. Persons with Sanfilippo syndrome have large amounts of a mucopolysaccharide called heparan sulfate in the urine.
Other tests may include:
Blood culture
Echocardiogram
Slit lamp eye exam
Skin fibroblast culture
X-rays of the bones
Treatment
There is no specific treatment available for Sanfilippo syndrome
Sanfilippo syndrome is an inherited disease of metabolism that makes the body unable to properly break down long chains of sugar molecules called glycosaminoglycans (formerly called mucopolysaccharides).
The syndrome belongs to a group of diseases called mucopolysaccharidoses (MPS). Specifically, it is known as MPS III.
See also:
MPS I H (Hurler syndrome)
MPS II, Hunter syndrome
MPS IV (Morquio syndrome)
MPS I S (Scheie syndrome)
Alternative Names
MPS III
Causes, incidence, and risk factors
Sanfilippo syndrome occurs when the substances (enzymes) needed to break down the heparan sulfate sugar chain are missing or are defective.
There are four main types of Sanfilippo syndrome, also called MPS III. Which type a person has depends on which enzyme is affected.
Sanfilippo type A is the most severe form. Persons with this type are missing or have an altered form of an enzyme called heparan N-sulfatase.
Sanfilippo type B occurs when a person is missing or doesn't not produce enough alpha-N-acetylglucosaminidase.
Sanfilippo C occurs when a person is missing or doesn't not produce enough acetyl-CoAlpha-glucosaminide acetyltransferase.
Sanfilippo D occurs when a person is missing or doesn't not produce enough N-acetylglucosamine 6-sulfatase.
The syndrome is inherited as an autosomal recessive trait. That means both your parents must pass you the defective gene in order for you to get this disease.
Sanfilippo syndrome is possibly the most common forms of MPS. It is seen in about 1 in 70,000 births. A family history of Sanfilippo syndrome increases one's risk for this condition.
Symptoms
Unlike other forms of MPS, symptoms appear after the first year of life. A decline in learning ability typically occurs between ages 2 and 6. The child may have normal growth during first few years, but final height is below average. Delayed development is followed by deteriorating mental status.
Other symptoms include:
Walking problems
Coarse facial features
Full lips
Heavy eyebrows that meet in the middle of the face above the nose
Diarrhea
Stiff joints that may not extend fully
Signs and tests
A physical exam may show signs of liver and spleen swelling. An eye exam will show clear corneas, unlike the cloudy corneas seen in persons with Hurler syndrome (MPS I H). Neurological testing will reveal signs of seizures and mental retardation.
Urine tests will be done. Persons with Sanfilippo syndrome have large amounts of a mucopolysaccharide called heparan sulfate in the urine.
Other tests may include:
Blood culture
Echocardiogram
Slit lamp eye exam
Skin fibroblast culture
X-rays of the bones
Treatment
There is no specific treatment available for Sanfilippo syndrome
MARFAN SYNDROME
What Is Marfan Syndrome?
Marfan syndrome is named after Antoine Marfan, the French doctor who first described the disorder in 1896. Marfan syndrome affects the body's connective tissue. Connective tissue is found everywhere in the body. Think of it as a sort of "glue" that helps support your organs, blood vessels, bones, joints, and muscles.
In people with Marfan syndrome, this "glue" is weaker than normal. That's because of a defect in the body's production of fibrillin (pronounced: fuh-brill-in), a special type of protein that's found in connective tissue. Weakened connective tissue can lead to problems in many parts of the body, especially the heart, eyes, and joints. For example, people with Marfan syndrome may have very loose, flexible joints as a result of these connective tissue problems.
Although Marfan syndrome has no cure (so the person will always have it), the good news is that doctors can treat just about all of its symptoms. Just a few decades ago, most people with the disease didn't live past 40. Now, thanks to new research and treatments, people with Marfan syndrome who are diagnosed early and get good medical care have about the same lifespan as everyone else.
What Causes It?
Marfan syndrome is pretty rare. It only happens to about 1 in every 5,000 people.
Marfan syndrome is a genetic disorder. Genetic disorders are caused by a change in genes that is either inherited (passed on from parent to child) or that happens during very early development in the womb. In the case of Marfan syndrome, a defect in a gene found on chromosome 15 causes problems in the production of fibrillin.
Although some genetic disorders can affect people of one gender or a particular ethnic heritage more than others, Marfan syndrome can affect both girls and guys from all ethnic backgrounds.
About 75% of the time, the gene for Marfan syndrome runs in families, getting passed down to children from parents who have the disease. A child born to a parent who has Marfan syndrome has a 50% chance of having the disease too.
In the remaining 25% of cases, though, neither parent has the disease. This means the genetic mutation responsible for causing Marfan syndrome occurs in either the egg or sperm cell at the time of conception. No one knows what causes this mutation, but once a child is born with Marfan syndrome, he or she then has a 50% chance of passing it on to his or her children.
What Are the Signs and Symptoms?
People who have Marfan syndrome tend to share certain physical traits:
They are often (but not always) much taller than their peers and have a lean, lanky build with disproportionately long arms and legs. Their fingers and toes are usually long and thin.
Their joints are loose and flexible.
They may have myopia (nearsightedness) or other vision problems (such as lens dislocation).
They may have certain facial characteristics, including a long, thin face; deep-set eyes; a small bottom jaw; a high, arched roof of the mouth; and crowded teeth.
Not everyone with these characteristics has Marfan syndrome, of course. Does your friend have it just because he is tall and thin? Probably not. If you're extremely nearsighted, does it mean you have the disorder? No again.
People who have Marfan syndrome have very specific symptoms that usually happen together. When these symptoms show up as a group, it alerts doctors to the possibility that a person might have the condition.
Other symptoms of Marfan syndrome can affect the skin and lungs. These symptoms are generally less common and less serious, especially in kids and teens.
Although people with Marfan syndrome often have similar physical features, the disease doesn't affect everyone in the same way. Some people have very mild symptoms, while others have severe ones - even within the same family. This is known as variable expression, and it makes it almost impossible to predict how the disease will progress in any affected individual.
How Do Doctors Diagnose It?
Several different types of doctors must be involved in diagnosing Marfan syndrome. They include a geneticist (a doctor who specializes in disorders of the genes), a cardiologist (heart doctor), an ophthalmologist (eye doctor), and an orthopedist (bone doctor).
A geneticist will ask whether anyone else in the family had similar symptoms - he or she may even ask if anyone in your family died early of a heart-related death. Then the geneticist will probably do some pretty painless exams, such as taking detailed skeletal measurements, including arm span (hold your arms out to your side - that's your arm span). This test can help because people with Marfan syndrome often have an arm span that's greater than their height.
The cardiologist will also do some painless tests. He or she may listen to the heart with a stethoscope to check for a murmur, then may order an X-ray of the chest, an electrocardiogram (or EKG, which measures electrical impulses in the heart), and an echocardiogram (a test that uses sound waves to produce a picture of the heart) to check the size of the aorta and to make sure the valves are functioning well.
An ophthalmologist will probably dilate the eye pupil with special drops then look into it with a slit lamp, a special type of microscope that can help detect lens dislocation and other eye problems.
An orthopedist will check for curvatures of the spine and breastbone, joint problems, and any other bone abnormalities.
If no one else in the family has the disorder, the patient has to show symptoms in three organ systems before doctors can diagnose Marfan syndrome.
Symptoms of Marfan syndrome may be apparent when a child is very young, while some people don't have noticeable symptoms until their teen years or even adulthood. But some people go through life never knowing they have the disease, and that can be dangerous. Getting diagnosed early means doctors can do a lot to help keep someone healthy.
What Can Happen if Marfan Syndrome Is Not Treated?
It's important to diagnose Marfan syndrome early because there can be serious complications when symptoms are not treated.
The most serious complication of Marfan syndrome involves the heart. Over time, the disorder can cause the aorta - the large artery that carries blood away from the heart to the body - to stretch and dilate (widen). This is called aortic dilation (pronounced: ay-or-tik dye-lay-shun) and if it's not treated, the aorta can eventually begin to tear, allowing blood to leak through. A large, sudden rupture can be fatal.
It's also common for people with Marfan syndrome to have problems with their heart valves. Instead of closing tightly, the valves, which help direct the flow of blood through the heart, can become floppy, causing blood to leak backward through the heart. Leaky heart valves cause the heart to work harder and become enlarged, so they must be carefully monitored.
Marfan syndrome may also cause problems with a person's eyes and skeleton. For example, people with the condition are more likely to get a detached retina (when the light-sensitive tissue at the back of the eye comes loose) or develop scoliosis (curvature of the spine). Again, the good news about these complications is that they can be prevented when Marfan syndrome is diagnosed and treated.
How Is It Monitored and Treated?
Teens with Marfan syndrome must be followed closely by a team of doctors. Because teens' bodies grow and change so quickly, most teens will need echocardiograms at least once a year, plus frequent eye and bone exams. This helps doctors stay on top of any new problems.
Many of the complications of Marfan syndrome can be managed with medications and, if necessary, surgery. Doctors may prescribe special medicines called beta blockers, which work to lower blood pressure and reduce wear and tear on the blood vessels. This can often delay the progression of aortic dilation. If the aorta does eventually widen to a potentially dangerous size, or if valve leakage becomes a problem, a doctor may recommend surgery to repair or replace the damaged parts of the heart.
Teens with Marfan syndrome who are nearsighted will probably have to wear glasses or contact lenses. If the lens of the eye becomes severely dislocated or if there are other complications, surgery may be necessary to fix eye problems.
Teens who develop scoliosis may have to wear a special back brace. Sometimes severe cases of scoliosis and chest wall problems may require surgery. Some people may also choose to have surgery for cosmetic reasons.
Anyone with heart problems associated with Marfan syndrome (especially anyone who's had heart surgery) should always take antibiotics before going to the dentist to prevent bacterial endocarditis, an infection of the walls of the heart caused when bacteria enter the bloodstream.
Teen girls with Marfan syndrome also need to be aware that pregnancy puts extra strain on the heart and may increase the risk of damage to the aorta. Teen girls with Marfan syndrome who are pregnant should talk to their doctor immediately.
Marfan syndrome is named after Antoine Marfan, the French doctor who first described the disorder in 1896. Marfan syndrome affects the body's connective tissue. Connective tissue is found everywhere in the body. Think of it as a sort of "glue" that helps support your organs, blood vessels, bones, joints, and muscles.
In people with Marfan syndrome, this "glue" is weaker than normal. That's because of a defect in the body's production of fibrillin (pronounced: fuh-brill-in), a special type of protein that's found in connective tissue. Weakened connective tissue can lead to problems in many parts of the body, especially the heart, eyes, and joints. For example, people with Marfan syndrome may have very loose, flexible joints as a result of these connective tissue problems.
Although Marfan syndrome has no cure (so the person will always have it), the good news is that doctors can treat just about all of its symptoms. Just a few decades ago, most people with the disease didn't live past 40. Now, thanks to new research and treatments, people with Marfan syndrome who are diagnosed early and get good medical care have about the same lifespan as everyone else.
What Causes It?
Marfan syndrome is pretty rare. It only happens to about 1 in every 5,000 people.
Marfan syndrome is a genetic disorder. Genetic disorders are caused by a change in genes that is either inherited (passed on from parent to child) or that happens during very early development in the womb. In the case of Marfan syndrome, a defect in a gene found on chromosome 15 causes problems in the production of fibrillin.
Although some genetic disorders can affect people of one gender or a particular ethnic heritage more than others, Marfan syndrome can affect both girls and guys from all ethnic backgrounds.
About 75% of the time, the gene for Marfan syndrome runs in families, getting passed down to children from parents who have the disease. A child born to a parent who has Marfan syndrome has a 50% chance of having the disease too.
In the remaining 25% of cases, though, neither parent has the disease. This means the genetic mutation responsible for causing Marfan syndrome occurs in either the egg or sperm cell at the time of conception. No one knows what causes this mutation, but once a child is born with Marfan syndrome, he or she then has a 50% chance of passing it on to his or her children.
What Are the Signs and Symptoms?
People who have Marfan syndrome tend to share certain physical traits:
They are often (but not always) much taller than their peers and have a lean, lanky build with disproportionately long arms and legs. Their fingers and toes are usually long and thin.
Their joints are loose and flexible.
They may have myopia (nearsightedness) or other vision problems (such as lens dislocation).
They may have certain facial characteristics, including a long, thin face; deep-set eyes; a small bottom jaw; a high, arched roof of the mouth; and crowded teeth.
Not everyone with these characteristics has Marfan syndrome, of course. Does your friend have it just because he is tall and thin? Probably not. If you're extremely nearsighted, does it mean you have the disorder? No again.
People who have Marfan syndrome have very specific symptoms that usually happen together. When these symptoms show up as a group, it alerts doctors to the possibility that a person might have the condition.
Other symptoms of Marfan syndrome can affect the skin and lungs. These symptoms are generally less common and less serious, especially in kids and teens.
Although people with Marfan syndrome often have similar physical features, the disease doesn't affect everyone in the same way. Some people have very mild symptoms, while others have severe ones - even within the same family. This is known as variable expression, and it makes it almost impossible to predict how the disease will progress in any affected individual.
How Do Doctors Diagnose It?
Several different types of doctors must be involved in diagnosing Marfan syndrome. They include a geneticist (a doctor who specializes in disorders of the genes), a cardiologist (heart doctor), an ophthalmologist (eye doctor), and an orthopedist (bone doctor).
A geneticist will ask whether anyone else in the family had similar symptoms - he or she may even ask if anyone in your family died early of a heart-related death. Then the geneticist will probably do some pretty painless exams, such as taking detailed skeletal measurements, including arm span (hold your arms out to your side - that's your arm span). This test can help because people with Marfan syndrome often have an arm span that's greater than their height.
The cardiologist will also do some painless tests. He or she may listen to the heart with a stethoscope to check for a murmur, then may order an X-ray of the chest, an electrocardiogram (or EKG, which measures electrical impulses in the heart), and an echocardiogram (a test that uses sound waves to produce a picture of the heart) to check the size of the aorta and to make sure the valves are functioning well.
An ophthalmologist will probably dilate the eye pupil with special drops then look into it with a slit lamp, a special type of microscope that can help detect lens dislocation and other eye problems.
An orthopedist will check for curvatures of the spine and breastbone, joint problems, and any other bone abnormalities.
If no one else in the family has the disorder, the patient has to show symptoms in three organ systems before doctors can diagnose Marfan syndrome.
Symptoms of Marfan syndrome may be apparent when a child is very young, while some people don't have noticeable symptoms until their teen years or even adulthood. But some people go through life never knowing they have the disease, and that can be dangerous. Getting diagnosed early means doctors can do a lot to help keep someone healthy.
What Can Happen if Marfan Syndrome Is Not Treated?
It's important to diagnose Marfan syndrome early because there can be serious complications when symptoms are not treated.
The most serious complication of Marfan syndrome involves the heart. Over time, the disorder can cause the aorta - the large artery that carries blood away from the heart to the body - to stretch and dilate (widen). This is called aortic dilation (pronounced: ay-or-tik dye-lay-shun) and if it's not treated, the aorta can eventually begin to tear, allowing blood to leak through. A large, sudden rupture can be fatal.
It's also common for people with Marfan syndrome to have problems with their heart valves. Instead of closing tightly, the valves, which help direct the flow of blood through the heart, can become floppy, causing blood to leak backward through the heart. Leaky heart valves cause the heart to work harder and become enlarged, so they must be carefully monitored.
Marfan syndrome may also cause problems with a person's eyes and skeleton. For example, people with the condition are more likely to get a detached retina (when the light-sensitive tissue at the back of the eye comes loose) or develop scoliosis (curvature of the spine). Again, the good news about these complications is that they can be prevented when Marfan syndrome is diagnosed and treated.
How Is It Monitored and Treated?
Teens with Marfan syndrome must be followed closely by a team of doctors. Because teens' bodies grow and change so quickly, most teens will need echocardiograms at least once a year, plus frequent eye and bone exams. This helps doctors stay on top of any new problems.
Many of the complications of Marfan syndrome can be managed with medications and, if necessary, surgery. Doctors may prescribe special medicines called beta blockers, which work to lower blood pressure and reduce wear and tear on the blood vessels. This can often delay the progression of aortic dilation. If the aorta does eventually widen to a potentially dangerous size, or if valve leakage becomes a problem, a doctor may recommend surgery to repair or replace the damaged parts of the heart.
Teens with Marfan syndrome who are nearsighted will probably have to wear glasses or contact lenses. If the lens of the eye becomes severely dislocated or if there are other complications, surgery may be necessary to fix eye problems.
Teens who develop scoliosis may have to wear a special back brace. Sometimes severe cases of scoliosis and chest wall problems may require surgery. Some people may also choose to have surgery for cosmetic reasons.
Anyone with heart problems associated with Marfan syndrome (especially anyone who's had heart surgery) should always take antibiotics before going to the dentist to prevent bacterial endocarditis, an infection of the walls of the heart caused when bacteria enter the bloodstream.
Teen girls with Marfan syndrome also need to be aware that pregnancy puts extra strain on the heart and may increase the risk of damage to the aorta. Teen girls with Marfan syndrome who are pregnant should talk to their doctor immediately.
GILBERTS SYNDROME
Gilbert's Syndrome is a disease of the Liver.There is a deficiency of an enzyme in the liver, which helps conjugate (attach) bilirubin (a by-product of haemoglobin breakdown) to a transporter molecule for excretion - hence there is an excess of bilirubin in the blood. This leads to no adverse effects in the patient but it leads to abnormal blood tests.
Who gets it?
This is a very common disorder with an incidence of 3-7%. However, because most people have no symptoms (asymptomatic) and it is usually picked up on a laboratory test - most people do not know they have it. It is more common in males than females.
Predisposing Factors
Gilbert's syndrome is a familial disorder, with 5-15% of patients having a family history of jaundice. Not all patients with the genetic defect in the enzyme become clinically jaundiced, however,the patient can become jaundiced during a mild illness.
Progression
The condition is usually diagnosed on a lab test by chance. Alternatively, patients may develop mild jaundice, especially during periods of fasting or mild illness.
Probable Outcomes
It is a completely benign (harmless) condition with no morbidity or increased risk of mortality. Patients naturally have a normal life expectancy.
How is it diagnosed?
Liver function tests - elevated bilirubin; otherwise normal.
Full blood count with peripheral smear, haptoglobin and reticulocyte count - there will be no evidence of red blood cell breakdown - another cause of high unconjugated bilirubin.
How is it treated?
No treatment required.
Who gets it?
This is a very common disorder with an incidence of 3-7%. However, because most people have no symptoms (asymptomatic) and it is usually picked up on a laboratory test - most people do not know they have it. It is more common in males than females.
Predisposing Factors
Gilbert's syndrome is a familial disorder, with 5-15% of patients having a family history of jaundice. Not all patients with the genetic defect in the enzyme become clinically jaundiced, however,the patient can become jaundiced during a mild illness.
Progression
The condition is usually diagnosed on a lab test by chance. Alternatively, patients may develop mild jaundice, especially during periods of fasting or mild illness.
Probable Outcomes
It is a completely benign (harmless) condition with no morbidity or increased risk of mortality. Patients naturally have a normal life expectancy.
How is it diagnosed?
Liver function tests - elevated bilirubin; otherwise normal.
Full blood count with peripheral smear, haptoglobin and reticulocyte count - there will be no evidence of red blood cell breakdown - another cause of high unconjugated bilirubin.
How is it treated?
No treatment required.
STICKLER SYNDROME
What is Stickler syndrome?
Stickler syndrome is a group of hereditary conditions characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and joint problems. These signs and symptoms vary widely among affected individuals.
A characteristic feature of Stickler syndrome is a somewhat flattened facial appearance. This is caused by underdeveloped bones in the middle of the face, including the cheekbones and the bridge of the nose. A particular group of physical features, called Robin sequence, is common in children with Stickler syndrome. Robin sequence includes an opening in the roof of the mouth (a cleft palate), a large tongue, and a small lower jaw. This combination of features can lead to feeding problems and difficulty breathing.
Many people with Stickler syndrome have severe nearsightedness (high myopia). In some types of this condition, the jelly-like substance within the eye (the vitreous) has an abnormal appearance. Other eye problems are also common, including increased pressure within the eye (glaucoma) and tearing of the lining of the eye (retinal detachment). These eye abnormalities can cause impaired vision or blindness in some cases.
Hearing loss is another feature of Stickler syndrome. The degree of hearing loss varies among affected individuals, and the loss may become more severe over time.
Most people with Stickler syndrome have skeletal abnormalities that affect the joints. For example, the joints of affected children and young adults may be loose and very flexible (hypermobile), though joints become less flexible with age. Arthritis often appears early in life and may cause joint pain or stiffness.
Researchers have described three types of Stickler syndrome, which are distinguished by their genetic cause and their characteristic signs and symptoms. In particular, the eye abnormalities and severity of hearing loss differ among the types. One type, often called non-ocular Stickler syndrome, does not affect the eyes.
Like Stickler syndrome, a condition called Marshall syndrome is characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and early-onset arthritis. Whether Marshall syndrome represents a variant form of Stickler syndrome or a separate disorder is controversial.
Stickler syndrome is a group of hereditary conditions characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and joint problems. These signs and symptoms vary widely among affected individuals.
A characteristic feature of Stickler syndrome is a somewhat flattened facial appearance. This is caused by underdeveloped bones in the middle of the face, including the cheekbones and the bridge of the nose. A particular group of physical features, called Robin sequence, is common in children with Stickler syndrome. Robin sequence includes an opening in the roof of the mouth (a cleft palate), a large tongue, and a small lower jaw. This combination of features can lead to feeding problems and difficulty breathing.
Many people with Stickler syndrome have severe nearsightedness (high myopia). In some types of this condition, the jelly-like substance within the eye (the vitreous) has an abnormal appearance. Other eye problems are also common, including increased pressure within the eye (glaucoma) and tearing of the lining of the eye (retinal detachment). These eye abnormalities can cause impaired vision or blindness in some cases.
Hearing loss is another feature of Stickler syndrome. The degree of hearing loss varies among affected individuals, and the loss may become more severe over time.
Most people with Stickler syndrome have skeletal abnormalities that affect the joints. For example, the joints of affected children and young adults may be loose and very flexible (hypermobile), though joints become less flexible with age. Arthritis often appears early in life and may cause joint pain or stiffness.
Researchers have described three types of Stickler syndrome, which are distinguished by their genetic cause and their characteristic signs and symptoms. In particular, the eye abnormalities and severity of hearing loss differ among the types. One type, often called non-ocular Stickler syndrome, does not affect the eyes.
Like Stickler syndrome, a condition called Marshall syndrome is characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and early-onset arthritis. Whether Marshall syndrome represents a variant form of Stickler syndrome or a separate disorder is controversial.
HURLER SYNDROME
Definition
Hurler syndrome is a rare, inherited disease of metabolism in which a person cannot break down long chains of sugar molecules called glycosaminoglycans (formerly called mucopolysaccharides).
Hurler syndrome belongs to a group of diseases called mucopolysaccharidoses, or MPS.
See also:
MPS II, Hunter syndrome
MPS IV (Morquio syndrome)
MPS III (Sanfilippo syndrome)
MPS I S (Scheie syndrome)
Alternative Names
Alpha-L-iduronate deficiency; Mucopolysaccharidosis type I; MPS I H
Causes, incidence, and risk factors
Persons with Hurler syndrome do not make a substance called lysosomal alpha-L-iduronidase. This substance, called an enzyme, helps break down long chains of sugar molecules called glycosaminoglycans (formerly called mucopolysaccharides). These molecules are found throughout the body, often in mucus and in fluid around the joints.
Without the enzyme, glycosaminoglycans build up and damage organs, including the heart. Symptoms can range from mild to severe.
Hurler syndrome is inherited, which means that your parents must pass the disease on to you. Both parents need to pass down the faulty gene in order for you to develop Hurler syndrome.
Hurler syndrome is a type of mucopolysaccharidosis called MPS I. Hurler syndrome is the most severe type. It is categorized as MPS I H.
The other subtypes of MPS I are:
MPS I H-S (Hurler-Scheie syndrome)
MPS I S (Scheie syndrome)
Symptoms
Symptoms of Hurler syndrome most often appear between ages 3 and 8. Infants with severe Hurler syndrome appear normal at birth. Facial symptoms may become more noticeable during the first 2 years of life.
Symptoms include:
Thick, coarse facial features with low nasal bridge
Halted growth
Progressive mental retardation
Cloudy corneas
Deafness
Joint disease, including stiffness
Heart value problems
Abnormal bones in the spine
Claw hand
Signs and tests
Urine tests are usually done first. These tests may show extra mucopolysaccharides, but they can't determine the specific form of MPS. More specific tests are done to diagnose the disease, including genetic testing for the alpha-L-iduronidase (IDUA) gene.
Other tests may include a spinal x-ray and EKG.
Treatment
Enzyme replacement therapy helps the body make alpha-L-iduronidase.
A bone marrow transplant can improve some of the symptoms of the disease. To prevent mental retardation, a bone marrow transplant probably should be done at a very young age.
Other treatments depend on the organs that are affected.
Hurler syndrome is a rare, inherited disease of metabolism in which a person cannot break down long chains of sugar molecules called glycosaminoglycans (formerly called mucopolysaccharides).
Hurler syndrome belongs to a group of diseases called mucopolysaccharidoses, or MPS.
See also:
MPS II, Hunter syndrome
MPS IV (Morquio syndrome)
MPS III (Sanfilippo syndrome)
MPS I S (Scheie syndrome)
Alternative Names
Alpha-L-iduronate deficiency; Mucopolysaccharidosis type I; MPS I H
Causes, incidence, and risk factors
Persons with Hurler syndrome do not make a substance called lysosomal alpha-L-iduronidase. This substance, called an enzyme, helps break down long chains of sugar molecules called glycosaminoglycans (formerly called mucopolysaccharides). These molecules are found throughout the body, often in mucus and in fluid around the joints.
Without the enzyme, glycosaminoglycans build up and damage organs, including the heart. Symptoms can range from mild to severe.
Hurler syndrome is inherited, which means that your parents must pass the disease on to you. Both parents need to pass down the faulty gene in order for you to develop Hurler syndrome.
Hurler syndrome is a type of mucopolysaccharidosis called MPS I. Hurler syndrome is the most severe type. It is categorized as MPS I H.
The other subtypes of MPS I are:
MPS I H-S (Hurler-Scheie syndrome)
MPS I S (Scheie syndrome)
Symptoms
Symptoms of Hurler syndrome most often appear between ages 3 and 8. Infants with severe Hurler syndrome appear normal at birth. Facial symptoms may become more noticeable during the first 2 years of life.
Symptoms include:
Thick, coarse facial features with low nasal bridge
Halted growth
Progressive mental retardation
Cloudy corneas
Deafness
Joint disease, including stiffness
Heart value problems
Abnormal bones in the spine
Claw hand
Signs and tests
Urine tests are usually done first. These tests may show extra mucopolysaccharides, but they can't determine the specific form of MPS. More specific tests are done to diagnose the disease, including genetic testing for the alpha-L-iduronidase (IDUA) gene.
Other tests may include a spinal x-ray and EKG.
Treatment
Enzyme replacement therapy helps the body make alpha-L-iduronidase.
A bone marrow transplant can improve some of the symptoms of the disease. To prevent mental retardation, a bone marrow transplant probably should be done at a very young age.
Other treatments depend on the organs that are affected.
OTOPALATODIGITAL SYNDROME
Otopalatodigital syndrome
Definition
Otopalatodigital (OPD) syndrome, also called digitootopalatal syndrome or palatootodigital syndrome, is a rare X-linked genetic disorder that affects bone and facial structure. OPD is fully expressed in males. Females are only mildly affected.
Description
There are two forms of OPD syndrome. Type I is inherited through an X-linked trait with intermediate expression in females while type II is inherited through an X-linked recesssive trait. OPD syndrome type I is also called Taybi syndrome. OPD syndrome type II is alternately called Andre syndrome, cranioorodigital syndrome, or faciopalatoosseous (FPO) syndrome.
A genetic disorder called frontometaphyseal dysplasia, or FMD, has very similar features to type I OPD syndrome.
There are three recognized forms of a genetic disorder called Larsen syndrome: an autosomal dominant type, a recessive type, and a lethal type. All three of these syndromes have similar symptoms to those seen in individuals affected with OPD syndrome. Recent evidence also suggests that Larsen syndrome, recessive type, may in fact be type II OPD syndrome.
As the various names of OPD syndrome suggest, this disorder is characterized by malformations and/or dysfunctions of the ears (-oto-), palate (-palato-), fingers and toes (-digito-), skull (-cranio-), mouth (-oro-), face (facio-), and bones (-osseo-). Some of the characteristics common to both types of OPD syndrome include: a cleft palate, a prominent forehead, a broad nose, widely spaced eyes (hypertelorism), a downward slanting of the opening between the upper and lower eyelids (palpebral fissures), conductive hearing loss, short fingers and toes (brachydactyly), an abnormal inward curving of the fingers (clinodactyly), a caved in chest at birth (pectus excavatum); short stature (dwarfism), and a congenital dislocation of the elbows caused by a misalignment of the head of the large bone in the forearm (radius).
Genetic profile
Both forms of OPD syndrome are X-linked. The gene mutation responsible for the appearance of type I OPD syndrome has been tentatively assigned to the Xq28 band. It is also believed that type II OPD syndrome is an allelic variant of type I OPD, which is to say that each form of OPD syndrome is caused by different mutations in the same gene or in overlapping genes at the same chromosomal location. Recessive type Larsen syndrome is also believed to be either another allelic variant of OPD syndrome, or identical to type II OPD syndrome. Another extremely rare genetic disorder, Melnick-Needles syndrome also has an overlapping of symptoms with type II OPD syndrome. It is felt that this syndrome is also possibly an allelic variant of OPD syndrome.
OPD syndrome is transmitted via the X chromosome. A female generally possesses two X chromosomes, one from her mother and one from her father. A male generally possesses only a single X chromosome, that from his mother. He gets a Y chromosome from his father. Certain rare exceptions to these inheritance patterns are seen, but in general, a female is an XX and a male is an XY. It is for this reason that X-linked disorders are generally seen in greater numbers of males than females. The male does not possess a second X chromosome that can be expressed. A male either has a mutation on his X chromosome, or he does not. A female, on the other hand, can be either homozygous or heterozygous for an X-linked trait. That is, she can either have two identical copies of this trait (homozygous) or only one copy is this trait (heterozygous).
Type I OPD syndrome is transmitted through a dominant trait. A child of a type I OPD syndrome affected parent has a 50% chance of also being affected with type I OPD syndrome.
Type II OPD syndrome is transmitted through an X-linked recessive trait. A child of a type II OPD syndrome affected parent has a 50% chance of also inheriting the gene for the type II OPD syndrome. Subsequently, if that child is male, he will have expression of the disorder. If it is a female child, then she generally will have milder features. Girls who are homozygous for type II OPD syndrome (inheriting the gene from each parent) will exhibit more severe symptoms than girls who are heterozygous for type II OPD syndrome. Males affected with type II OPD syndrome exhibit symptoms similar to those seen in homozygous girls.
Demographics
As of early 2001, the incidence of occurrence of both forms of OPD syndrome has not been determined. The lack of occurrence rate data is partially due to the fact that type I OPD syndrome can often have only very mild clinical and radiological symptoms, such that it is often not diagnosed, or even noticed, until type I OPD syndrome is recognized in a more severely affected member of the family.
Type I OPD syndrome is more common than type II OPD syndrome, and as of early 2001, nearly 300 cases had been reported in the medical literature. In 1996, only 25 detailed cases of type II OPD syndrome had been described in the medical literature.
Signs and symptoms
The severity of symptoms experienced by those people affected with OPD syndrome varies widely from practically asymptomatic to symptoms so severe that they cause infantile or prenatal death. In type II OPD syndrome, males are generally affected with far more severe symptoms than females.
There are six abnormalities of the face and head that characterize OPD syndrome: a cleft palate, downwardly slanting openings between the eyelids, widely spaced eyes (hypertelorism), a prominent forehead, a broad nose, and conductive hearing loss.
Conductive hearing loss results from a blockage of the auditory canal or some other dysfunction of the eardrum or one of the three small bones within the ear (the stapes, the malleus, and the incus) that are responsible for collecting sound. In this type of hearing loss, the auditory nerve is normal. In individuals affected with OPD syndrome, complete deafness from birth is often observed. In those individuals with partial hearing, speech disabilities related to this hearing loss are quite common.
In addition to the abnormalities of the head, universal characteristics of OPD syndrome affected individuals also include: abnormally short fingers and toes (brachydactyly); abnormal inward curving of some fingers (clinodactyly); short nails; a congenital dislocation of the elbows, and sometimes the knees; a caved in chest (pectus excavatum) at birth; and, growth retardation.
Symptoms that are characteristic of type I OPD syndrome include: curvature of the spine (scoliosis); generalized bone malformation, particularly in the bones of the limbs and ribcage; broad distal digits, malformed or missing teeth (hypodontia); and, mild mental retardation.
Symptoms that are characteristic of type II OPD syndrome include: low-set ears, flattened vertebrae in the spine, bowing of the bones of the limbs, flexed overlapping digits, a malformation or complete absence of the large bone in the shin (fibula), malformations of the hips, a small opening in the abdominal wall (hernia) at the navel (omphalocele), and a malformation of the male genitalia in which the opening of the urethra is located on the underside of the penis, rather than at the tip of the penis (hypospadias).
Diagnosis
A diagnosis of OPD syndrome is suggested when a patient presents the five characteristic abnormalities of the head and face accompanied by conductive hearing loss. This diagnosis is confirmed by the observance of brachdactyly and congenital dislocation of the elbows and/or knees.
Type I OPD syndrome is differentially diagnosed from type II OPD syndrome by the appearance of scoliosis. Type II OPD syndrome is differentially diagnosed from type I OPD by the presence of an omphalocele and greater malformations of the bones of the ribcage.
Treatment and management
There are currently no treatments aimed specifically at OPD syndrome. Instead, treatment is on a case-by-case and symptom-by-symptom basis.
Malformations of the head and face can generally be corrected, if necessary, by surgeries. In certain instances, the conductive hearing loss experienced by individuals with OPD syndrome may also be corrected through surgery. When it cannot, hearing aids may be required.
Many of the skeletal abnormalities seen in OPD syndrome affected individuals can either be corrected by surgery or can be alleviated through the use of braces until the bones become more fully developed.
Malformations of the male genitalia and the omphalocele observed in type II OPD syndrome affected infants can also be corrected by surgery.
Certain OPD affected individuals may also benefit from treatments with growth hormone.
In cases of mild mental retardation or speech problems, early intervention programs for these types of developmental delays may also be of benefit.
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