Thank you for everyone who helped me with my work especially my family for reducing pressure I had.

Dedication & Acknowledgements

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Abstract

Purpose / Goal

Genetic Disorder Syndrome

In Korea, there are 50 million people who su�er from rare genetic disorder and there are about 110 species of those diseases. For there rarity, these patients have nothing to do but relying on expensive imported medi-cal products, su�ering both mentally, physically, and economically. In Japan, they are taking care of 44 types of diseases whereas in Korea not even accurate statics of number of patients are recorded.

First of all, I had no actual knowledge of science especially biology. �rough this opportunity I wanted to gain more knowledge about genes and also two of my relatives had passed away from genetic cancer, but since my family didn’t know anything about genetic disorder we had nothing to do but getting involved in medical insurance. A�er I have �nished my research and thesis I could give out some of the information.

Conclusion

Have people ever said to you, "It’s in your genes." �ey were probably talking about a physical characteristic, talent that people share with other members of the family. We know that genes play an important role in deciding how we look and act and even whether we get sick. Now, scientists are trying to use that knowledge in other ways, such as preventing and treating health problems. Most living organisms are made up of cells that contain a substance called DNA. DNA is wrapped together and form chromosomes. Most cells in the human body have 23 pairs of chromosomes, in total there are 46. However, individual sperm and egg cells, have just 23 unpaired chromosomes. People receive half of their chromosomes from their mother's egg and receive the other from their father's sperm cell. A male child receives a X chromosome from his mother and Y chromosome from his father and females get a X chro-mosome both her mother and father. Genes are sections or segments of DNA that are carried on the chromosomes and decide speci�c human characteristics or features, such as how tall they are or what hair color they have. Because each parents gives their child one chromosome in each pair, they have two genes except for some of the genes on the X and Y chromosomes in boys because they have only one of each. Some characteristics come from a single gene, when others come from gene combinations. Because every people have 25,000 to 35,000 di�erent genes each, there are tremendous amount of numbers of combinations. Also, heredity is the passing of genes from one generation to the next. People inherit their parent's genes. Cells are very small and invisible to humans' naked eyed and each cell in body contains about 6 feet of DNA thread, in total there are about 3 billion miles. DNA patterns are the codes for producing proteins, chemicals that enable humans' body to work and grow. Genes hold the instructions for making protein products such as the enzymes to digest food or the pigment that gives your eyes their color. As children's cells split, they pass this genetic information to the new cell. Genes can be superior to the others. Superior genes show their e�ect even if there is only one copy of that gene in the pair. For a person to have a recessive disease or characteristic, the person must have the gene on both chromosomes of the pair. Cells can sometimes contain changes in the information in their genes. �is is called gene mutation, and it is o�en occur when cells are growing old or had been exposed to chemicals or radiations. Fortunately, cells usually recognize these mutations and repair them by themselves. However, they can cause illnesses, such as some types of cancer. And if the gene mutation exists in egg or sperm cells, children can inherit the mutated gene from their parents. But having a genetic mutation that may cause disease doesn't always mean that a person will actually get that disease. Because people inherit a gene from each parent, having one disease gene usually does not cause any problems because the normal gene can allow people's body to make the normal protein it needs. If one person carries the dominant gene for a disease, he or she will usually have the

disease and each of the person's children will have 50% chance of inheriting the gene and getting the disease. Diseases caused by dominant genes include several diseases such as syndromes, which I will talk further about.

Background InformationMarfan Syndrome

De�nition

Marfan syndrome is named a�er Antoine Marfan, the French doctor who �rst described the disorder in 1896. Marfan syndrome a�ects the body's connective tissue. Connective tissue is found everywhere in the body. �ink 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. �at's because of a defect in the body's production of �brillin 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, �exible joints as a result of these connective tissue problems.

Although Marfan syndrome has no cure 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.

Cause

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 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 �brillin. Although some genetic disorders can a�ect people of one gender or a particular ethnic

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heritage more than others, Marfan syndrome can a�ect 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. �is 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 a child born with Marfan syndrome then has a 50% chance of passing it on to his or her children.

Symptoms

-�ey are o�en much taller than their peers and have a lean, lanky build with dispropor-tionately long arms and legs. �eir �ngers and toes are usually long and thin. -�eir joints are loose and �exible. -�ey may have myopia or other vision problems. -�ey 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.

Diagnosis

Several di�erent types of doctors must be involved in diagnosing Marfan syndrome. �ey include a cardiologist, an ophthalmologist and an orthopedist A geneticist will ask whether anyone else in the family had similar symptoms and may even ask if anyone in your family died early of a heart-related death. �en the geneticist will probably do some pretty painless exams, such as taking detailed skeletal measurements, including arm span �is test can help because people with Marfan syndrome o�en have an arm span that's greater than their height. �e 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 and an echocardiogram 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 prob-lems, 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.

Treatments

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. �is helps doctors stay on top of any new problems.

vessels. �is can o�en 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 �x 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 syndromeshould 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.

Many of the complications of Marfan syndrome can be managed with medications and, if necessary, surgery. Doctors may prescribe special medicines called beta blockers and ACE inhibitors, which work to lower blood pressure and reduce wear and tear on the blood

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Turner syndrome (TS) is a medical disorder that a�ects about 1 in every 2,500 girls. Although researchers don't know exactly what causes Turner syndrome, they do know that it's the result of a problem with a girl's chromosomes.

Most girls are born with two X chromosomes, but girls with Turner syndrome are born with only one X chromosome or they are missing part of one X chromosome. �e e�ects of the condition vary widely among girls with Turner syndrome. It all depends on how many of the body's cells are a�ected by the changes to the X chromosome.

Girls with Turner syndrome are usually short in height. Girls with Turner syndrome who aren't treated for short stature reach an average height of about 4 feet 7 inches (1.4 meters). �e good news is that when Turner syndrome is diagnosed while a girl is still growing, she can be treated with growth hormones to help her grow taller.

In addition to growth problems, Turner syndrome prevents the ovaries from developing properly, which a�ects a girl's sexual development and the ability to have children. Because the ovaries are responsible for making the hormones that control breast growth and menstrua-tion, most girls with Turner syndrome will not go through all of the changes associated with puberty unless they get treatment for the condition. Nearly all girls with Turner syndrome will be infertile, or unable to become pregnant on their own.

E�ects

A number of other health problems occur more o�en in girls with Turner syndrome, including kidney problems, high blood pressure, heart problems, overweight, hearing di�cul-ties, diabetes, and thyroid problems. Some girls with the condition may experience learning di�culties, particularly in math. Many have a di�cult time with tasks that require skills such as map reading or visual organization.

In addition to short stature and lack of sexual development, some of the other physical features commonly seen in girls with Turner syndrome are:

a "webbed" neck (extra folds of skin extending from the tops of the shoulders to the sides of the neck) a low hairline at the back of the neck drooping of the eyelids di�erently shaped ears that are set lower on the sides of the head than usual

Turner Syndrome

De�nition

abnormal bone development (especially the bones of the hands and elbows) a larger than usual number of moles on the skin edema or extra �uid in the hands and feet Diagnose

Girls with Turner syndrome are usually diagnosed either at birth or around the time they might be expected to go through puberty. If a baby girl has some of the signs of Turner syndrome, a doctor will usually order a special blood test called a karyotype. �e test counts the number of chromosomes and can identify any that are abnormally shaped or have missing pieces. In some cases, there are no recognizable signs that a girl has the condition until she reaches the age at which she would normally go through puberty.

If the karyotype blood test reveals that a girl has Turner syndrome, her doctor may order additional tests to check for problems with the kidneys, heart, hearing, and other problems that are o�en associated with Turner syndrome.

Treatments

Because Turner syndrome is a condition that is caused by a chromosomal abnormality, there's no speci�c cure. However, scientists have developed a number of treatments that can help correct some of the problems associated with the condition - such as growth problems - and researchers are constantly looking into new forms of treatment.

Growth hormone treatment can improve growth and in�uence a girl's �nal adult height. In fact, in many cases, the treatment can help many girls with Turner syndrome reach a �nal height in the average range, especially if treatment is started early enough in childhood.

Another treatment for Turner syndrome is estrogen replacement, which helps the girl develop the physical changes of puberty, including breast development and menstrual periods. �is treatment is o�en started when a girl reaches about age 12 or 13.

And a technique called in vitro fertilization can make it possible for some women with Turner syndrome to become pregnant. A donor egg can be used to create an embryo, which is then put into the uterus of the woman with Turner syndrome. With proper supportive care, the woman can carry the pregnancy to term and deliver a baby through the normal birth process.

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Down syndrome (DS), also called Trisomy 21, is a condition in which extra genetic mate-rial causes delays in the way a child develops, both mentally and physically. It a�ects about 1 in every 800 babies.

�e physical features and medical problems associated with Down syndrome can vary widely from child to child. While some kids with DS need a lot of medical attention, others lead healthy lives.

�ough Down syndrome can't be prevented, it can be detected before a child is born. �e health problems that can go along with DS can be treated, and there are many resources within communities to help kids and their families who are living with the condition.

Cause

Normally, at the time of conception a baby inherits genetic information from its parents in the form of 46 chromosomes: 23 from the mother and 23 from the father. In most cases of Down syndrome, a child gets an extra chromosome 21 — for a total of 47 chromosomes instead of 46. It's this extra genetic material that causes the physical features and developmen-tal delays associated with DS.

Although no one knows for sure why DS occurs and there's no way to prevent the chromo-somal error that causes it, scientists do know that women age 35 and older have a signi�cantly higher risk of having a child with the condition. At age 30, for example, a woman has about a 1 in 900 chance of conceiving a child with DS. �ose odds increase to about 1 in 350 by age 35. By 40 the risk rises to about 1 in 100.

Treatments

- Nuchal translucency testing. �is test, performed between 11 and 14 weeks of pregnancy, uses ultrasound to measure the clear space in the folds of tissue behind a developing baby's neck. (Babies with DS and other chromosomal abnormalities tend to accumulate �uid there, making the space appear larger.) �is measurement, taken together with the mother's age and the baby's gestational age, can be used to calculate the odds that the baby has DS. Nuchal trans-lucency testing is usually performed along with a maternal blood test.

- �e triple screen or quadruple screen (also called the multiple marker test). �ese tests measure the quantities of normal substances in the mother's blood. As the names imply, triple screen tests for three markers and quadruple screen includes one additional marker and is more accurate. �ese tests are typically o�ered between 15 and 18 weeks of pregnancy.

Down Syndrome

De�nition

-Integrated screen. �is uses results from �rst trimester screening tests (with or without nuchal translucency) and blood tests with second trimester quad screen to come up with the most accurate screening results.

- A genetic ultrasound. A detailed ultrasound is o�en performed at 18 to 20 weeks in conjunction with the blood tests, and it checks the fetus for some of the physical traits abnor-malities associated with Down syndrome.

Crouzon Syndrome

De�nition

Crouzon syndrome is a genetic disorder characterized by the premature fusion of certain skull bones (craniosynostosis). �is early fusion prevents the skull from growing normally and a�ects the shape of the head and face.

Many features of Crouzon syndrome result from the premature fusion of the skull bones. Abnormal growth of these bones leads to wide-set, bulging eyes and vision problems caused by shallow eye sockets; eyes that do not point in the same direction (strabismus); a beaked nose; and an underdeveloped upper jaw. In addition, people with Crouzon syndrome may have dental problems and hearing loss, which is sometimes accompanied by narrow ear canals. A few people with Crouzon syndrome have an opening in the lip and the roof of the mouth (cle� lip and palate). �e severity of these signs and symptoms varies among a�ected people. People with Crouzon syndrome are usually of normal intelligence.

Cause

�is condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is su�cient to cause the disorder.

In some cases, an a�ected person inherits the mutation from one a�ected parent. Other cases result from new mutations in the gene and occur in people with no history of the disor-der in their family.

Treatments

A�er examining an infant, it is easy to diagnose Crouzon Syndrome. Xrays, magnetic resonance imaging (MRIs) and genetic testing are used to con�rm the diagnosis.

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Conclusion

Surgery is used to prevent the cranial sutures from fusing and damaging brain develop-ment. Besides cranial surgical intervention, extensive facial, orthodontic and cosmetic surgery is also required.

�ere are many medical experts involved in the treatment of Crouzon Syndrome - Neuro-surgeons, Neuroradiologists, Orthodontists, Dentists and Ophthalmologists.

Even though it was di�cult to understand genetic disorder fully, it seemed like there weren’t much accurate information sited on the websites. Lots of patients were waiting for treatments and �nancial supports. I hope that more people will give more attentions for those who need lot of care.

* Adachi M, Asakura Y, Matsuo M, Yamamoto T, Hanaki K, Arlt W. POR R457H is a global founder mutation causing Antley-Bixler syndrome with autosomal recessive trait. Am J Med Genet A. 2006; 140: 633–5. [PubMed]

* Akai T, Yamamoto K, Iizuka H, Kawakami S, Yoshida J, Kakinuma H, Yaguchi Y, Ozawa T. Syndromic craniosynostosis with elbow joint contracture. Pediatr Neurosurg. 2006; 42: 108–12. [PubMed]

* Anderson J, Burns HD, Enriquez-Harris P, Wilkie AOM, Heath JK. Apert syndrome mutations in �broblast growth factor receptor 2 exhibit increased a�nity for FGF ligand. Hum Mol Genet. 1998; 7: 1475–83. [PubMed]

* Anderson PJ, Netherway DJ, Cox TC, Roscioli T, David DJ. Do Craniosynostosis syndrome phenotypes with both FGFR2 and TWIST mutations have a worse clinical outcome? J Craniofac Surg. 2006; 17: 166–72. [PubMed]

* Baroni T, Carinci P, Lilli C, Bellucci C, Aisa MC, Scapoli L, Volinia S, Carinci F, Pezzetti F, Calvitti M, Farina A, Conte C, Bodo M. P253R �broblast growth factor receptor-2 mutation induces RUNX2 transcript variants and calvarial osteoblast di�erentiation. J Cell Physiol. 2005; 202: 524–35. [PubMed]

* Bellus GA, Gaudenz K, Zackai EH, Clarke LA, Szabo J, Francomano CA, Muenke M. Identical mutations in three di�erent �broblast growth factor receptor genes in autosomal dominant craniosynostosis syndromes. Nat Genet. 1996; 14: 174–6. [PubMed]

* Benacerraf BR, Spiro R, Mitchell AG. Using three-dimensional ultrasound to detect craniosynostosis in a fetus with Pfei�er syndrome. Ultrasound Obstet Gynecol. 2000; 16: 391–4. [PubMed]

* Biesecker LG. Strike three for GLI3. Nat Genet. 1997; 17: 259–60. [PubMed]

* Binaghi S, Gudinchet F, Rilliet B. Three-dimensional spiral CT of craniofacial malformations in children. Pediatr Radiol. 2000; 30: 856–60. [PubMed]

* Bottero L, Cinalli G, Labrune P, Lajeunie E, Marchac D, Renier D. [Antley-Bixler syndrome. Description of two new cases and review of the literature. Prognostic and therapeutic aspects] Ann Chir Plast Esthet. 1997; 42: 48–55. [PubMed]

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Reference