06 분당분원 - 손승연
(Chrity) 손승연
Genetic Disorders Klinefelter’s Syndrome and Albinism
Dedication
First of all, I spent a lot of time completing my thesis. erefore, I would like to dedicate my thesis to myself. Secondly, my parents provided me many ideas on this particular topic and tried to let me work on my thesis as comfortably as possible. us, I dedicate my thesis to my parents. Next, my teacher, Mi-Ran Lee has advised me on my writing and read this long thesis just for me to improve my skills. ere- fore, I dedicate my thesis to Miss Lee. (Or, maybe in the near future, Mrs. Lee!) Most importantly, there are numerous professionals that provided me the information I needed to write my thesis. I also dedicate my thesis to all of them. Everyone thanks a lot. List Of Tables
(Table 1) Symptoms of the variants of Klinefelter’s Syndrome1 Chromosome complement Phenotype Klinefelter syndrome but tends to be milder - e presence of a proportion of normal cells reduces the risk of developmental delay 46XY/47XXY and fertility may be possible - Testosterone treatment may not be indicated - Boys tend to be taller with long lower extremities 48XXYY - IQ is generally reduced with speech and motor delay more commonly occurring - May result in a more abnormal phenotype with hypertelorism, epicanthic folds, simple ears and mild prognathism. 48XXYY - Stature is tall and there may be skeletal abnormalities including clinodactyly, elbow abnormalities, and radioulnar synostosis. - Mild to moderate mental retardation associated with a passive personality is o en observed
(Table 2) Features of Klinefelter’s Syndrome1
Growth and · Neonates with Klinefelter syndrome are generally unremarkable with normal growth parameters feeding · Height velocity tends to be increased by 5 years of age ; therefore, individuals tend to be taller than their peers, with an increase in leg length · Slight delay in motor development possible - approximately two thirds have a delay in walking · Language milestones may also be delayed, particularly when compared to siblings Development · By 4 years of age, verbal-intellectual skills lag behind nonverbal skills and behavior · Overall IQ tends to be lower than that of siblings · However, development is variable with some boys showing no delay at all · Shyness, lack of assertiveness and immaturity are common features - the delay in language skills is thought to be a contributing factor · Aggressive behaviour has been reported due to frustration, but is not characteristic Personality · Some report an increased incidence of attention de cit and hyperactivity disorder characteristics · Adolescents may lack con dence, which can limit academic and physical success · Due to problems in childhood, some individuals may experience social and emotional problems later in life · Sexual development is normal in infancy and childhood · e normal adolescent elevation of testosterone tends to plateau at 14 years of age. Serum levels remain low and so by mid-puberty, FSH and LH gonadotrophin levels have risen · Testicular growth is arrested, resulting in a reduced testicular size throughout adulthood Endocrine · Progressive hyalinisation and brosis and reduced number of Leydig cells result in low levels of testosterone and infertility · Sexual function is normal but the ejaculate contains no sperm · Gynacomastia can occur in adolescents, which may or may not regress · Although facial, axillary and pubic hair growth is observed, this is to a lesser extent than would be expected in normal males
1 NHS Evidence. “Klinefelter Syndrome.” NHS Evidence. Oct 2005. < http://www.library.nhs.uk/geneticconditions/viewresource.aspx?resID=104897 > 08 분당분원 - 손승연
· Increased incidence of mitral valve prolapse, as well as an increased risk of cardiovascular disease due to increased cholesterol levels - can be reduced with testosterone treatment Cardiovascular · Research indicates an increased incidence of chronic leg ulcers, possibly associated with testosterone de ciency or vascular abnormality · ere is an increased incidence of certain autoimmune diseases including systemic Immunological lupus erythematosis, diabetes mellitus and thyroid disturbances · Recent studies have not shown an overall increased risk of cancer in klinefelters syndrome. however there is an increased incidence (<1%) of extragonadal germ cell tumours : Neoplasia - Usually occur in the mediastinum - Individuals may present with respiratory symptoms, particularly between adolescence and the age of 30 - In younger boys these tumours may result in precocious puberty
Dental · Taurodontism (enlarged tooth size with reduced root size) and early tooth decay may occur
(Table 3) Patients of Albinism2 (Table 4) Patients of Albinism3 (Table 5) Albino Dolphin4
2 Author Unknown. “Albinism.” Google. Date Unknown.
Because most genetic disorders are rare, the patients o en get much attention, which is more negative than positive. I think that those patients getting such treatments are unfair. erefore, I made up my mind to have accurate knowledge about the genetic disorders and understand them with objectivity, especially Klinefelter’s syndrome and albinism. First, I introduced what are genetic disorders. Second, I researched about the frequency, causes, symptoms, and treatments of Klinefelter’s syndrome. ird, I researched about frequency, causes, diagnosis, symptoms, treatments, and lives of the patients of albinism.
Introduction
In the book named
I love fantasy novels, especially those with characters who have colorful hair and eyes. en one day, my school science teacher told us about albinism. She said that because of the problems in their pigment, people with albinism are di erent in appearance with us, such as white hair and red eyes. When I heard it, I was surprised that people who seem like they just popped up from the fantasy books actually exist. I came back home and browsed Albinism on the Internet. ere are some images, and I thought it was beautiful but in the same time can be painful to the patients.
Klinefelter’s syndrome and albinism are both rare genetic disorders. I assume not much people have seen the patients of Klinefelter’s syndrome or albinism around them. As a result, the patients receive much attention, which is more negative than positive. And of course, they su er a lot from such interest. I saw the videos in YouTube, which are taken by one girl (ID 10N3star) who has 10 분당분원 - 손승연
albinism. She talks about basic information and common misconceptions of albinism. From her candid speeches, I realized that perceptions of people are more serious than what I thought.
I think that those patients getting such treatments are unfair. ey didn’t want the genetic disorders; it’s just the abnormalities in their genes, and those are out of their willpower. erefore, I made up my mind to have accurate knowledge about the genetic disorders and understand them with objectivity. Of various genetic disorders, I chose Klinefelter’s syndrome and albinism, which are usually well-known by people and are more likely to happen than other genetic disorders.
First, I introduced what genetic disorders are. Second, I researched about the frequency, causes, symptoms, and treatments of Klinefelter’s syndrome. ird, I researched about frequency, causes, diagnosis, symptoms, treatments, and lives of the patients of albinism.
Body
Genetic Disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes. Most disorders are quite rare and a ect one person in every several thousands or millions. Genetic disorders may also be complex, multifactorial or polygenic, this means that they are likely associated with the e ects of multiple genes in combination with lifestyle and environmental factors. Multifactoral disorders include heart disease and diabetes. Although complex disor- ders o en cluster in families, they do not have a clear-cut pattern of inheritance. is makes it dicult to determine a person’s risk of inheriting or passing on these disorders. Complex disor- ders are also dicult to study and treat because the speci c factors that cause most of these disorders have not yet been identi ed. Among the most well-known genetic disorders, there are asthma, autism, autoimmune diseases such as multiple sclerosis, cancers, cle palate, diabe- tes, heart disease, hypertension, inammatory bowel disease, mental retardation, and obesity.
A single gene disorder is the result of a single mutated gene. ere are estimated to be over 4000 human diseases caused by single gene defects. Single gene disorders can be passed on to subsequent generations in several ways. ey can be classi ed into categories of autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, Y-linked, and mito- chondrial single gene disorders.
Klinefelter’s Syndrome
In 1942, Dr. Harry Klinefelter and his coworkers at the Massachusetts General Hospital in Boston published a report about nine men who had enlarged breasts, sparse facial and body hair, small testes, and an inability to produce sperms. By the late 1950s, researchers discovered that men with Klinefelter’s syndrome, as this group of symptoms came to be called, had an extra sex chromosome, XXY instead of the usual male arrangement, XY5.
Not all males with an XXY chromosome pattern have the symptoms of Klinefelter’s syndrome 6. Many men live out their lives without ever even suspecting that they have additional chromosomes. "I never refer to newborn babies as having Klinefelter's, because they don't have a syndrome," said Arthur Robinson M.D., a pediatrician at the University of Colo- rado Medical School in Denver and also the director of the NICHD-sponsored study of XXY males. "Presumably, some of them will grow up to develop the syndrome Dr. Klinefelter described, but a lot of them won't.” For this reason, the term "Klinefelter syndrome" has fallen out of favor with medical researchers. Most prefer to describe men and boys having the extra chromosome as "XXY males."5 Moreover, the term XXY condition is used to describe the symptoms of Klinefelter’s syndrome6.
Klinefelter’s syndrome is the most common sex chromosome disorder and the second most common condition caused by extra chromosomes 7. It a ects 1 in 500~1,000 males. Most variants of Klinefelter’s syndrome are much rarer, occurring in 1 in 50,000. However, Klinefelter’s syndrome does not occur in females 8. e variants such as XXYY, XXXY, XXXYY, XXXXY, and mosaicism (only a proportion of cells have an abnormal chromosome number1) are much rarer 10.10 Women who have pregnancies a er age 35 are slightly more likely to have a boy with this syndrome than younger women 9.
6 National Institute of Child Health and Human Development (NICHD). "Klinefelter Syndrome." NICHD-The Eunice Kennedy Shriver National Institute of Child Health and Human Development O cial Home Page. 24 May 2007.
Symptoms
As mentioned above, not all males with the XXY condition have the same symptoms or to the same degree. e symptoms depend on how many XXY cells the patient has, how much testosterone his body has, and when his age of diagnosis is. e XXY condition can a ect three main areas of development: rst; physical development, second; language development, and third; social development.6
First, XXY males are di erent physically with normal males. As babies, many XXY males have weak muscles and weak strength. ey may sit up, crawl, and walk later than other infants. A er about age 4, they tend to be taller and may have less muscle control and coordi- nation than other boys of their age.6 e start of puberty in XXY males are usually late than other boys.10 By adulthood, XXY males are o en taller, have lanky, youthful build and facial appearance, have a rounded body type,11 have increased levels of hormones called gonadotro- pins, which are common in XXY males.5
Usually, XXY males are taller, weaker, have less facial and body hair, have longer limbs, have larger breasts, have small testes, have broader hips, have weaker bones, and have lower energy level than normal males. Because they o en don’t make as much testosterone as other males, they usually make little or no sperms and thus 95 to 99 percent of them are infertile. Also, they are more likely than other men to have certain health problems such as tooth decay, autoimmune disorders, breast cancer, vein diseases, and osteoporosis. (Osteoporosis is a condition in which the bones become weak and are easily broken, and it usually occurs when people get older or do not eat certain substances enough.)6 In contrast to these potentially increased risks, it is currently thought that rare X-linked recessive conditions occur less frequently in XXY males than in normal XY males, since these conditions are transmitted by genes on the X chromosome, and people with two X chromosomes are typically only carriers rather than a ected by these X-linked recessive conditions.11 Moreover, 25% of them show mental retardation, and the possibility of conduct disorder is even higher.10
XXY males have some degree of gynecomastia, or breast enlargement due to the increase of breast tissue.11 Gynecomastia is present to some extent in about a third of a ected individu- als, a slightly higher percentage than in the XY population, but only about 10% of XXY males' gynecomastia is noticeable enough to require surgery.5
10 Encyclopedia Britannica. “Klinefelter’s syndrome.” Daum. Date Unknown.
Second, XXY males are di erent with other boys in the aspect of language development. As boys, between 25 to 85 percent of XXY males have some kind of language problem, such as learning to talk late, troubles expressing their thoughts and needs, troubles reading, listening, and processing what they hear, and troubles in vocabulary. When they become adults, XXY males may have a harder time doing work that involves reading and writing.6
ird, XXY males have dissimilar social development as normal males. According to Dr. Robinson, the director of the NICHD-funded study, XXY babies tend to start life as what many parents call "good" babies : quiet, undemanding, and perhaps even a little passive. When they grow up little more, XXY males tend to be shy and reserved.5 When they get older, they are usually quieter, shier, less self-con dent, less active, less likely to show a leadership, more supportive, and obedient than other boys. ey may struggle in school and sports, which means that they may have more trouble tting in with other kids and thus require special social skills training program. However, in adulthoods, XXY males live usual lives: they have friends, even though usually a few, families, and normal social relationships.6
e variants have similar symptoms with Klinefelter’s Syndrome, but the degrees are more severe. In general, the extent of phenotypic abnormalities, including mental retardation, is related directly to the number of supernumerary X chromosomes. As the number of X chro- mosomes increases, somatic and cognitive development are more likely to be a ected. More- over, mental capacity diminishes with additional X chromosomes. (For speci c symptoms of the variants, see Table 1.) (For the summarized table of the symptoms of Klinefelter’s syndrome, see Table 2.) 14 분당분원 - 손승연
Treatments
e XXY chromosomes pattern can not be changed. But there are various ways to treat the symptoms of the XXY condition, including educational, therapeutic, and medical options. One of the most important factors for all types of treatment is starting it as early in life as possible.6
First, there are some educational treatments for XXY males. When they are young, many XXY males qualify for special treatments from school and teachers.6 Teachers can help those XXY boys by even little attention and caution.
XXY males o en have decreased immediate auditory recall they have trouble remembering what they have just heard. Parents and teachers can help them remember by approaching memory through visual channels. Illustrating words with pictures may help. Gesturing is another useful technique. For example, a teacher might accompany the word "yes" with a nod of the head. Similarly, shaking the head from side to side is the universal gesture for "no." Other useful gestures include waving goodbye, showing the child an upraised palm to indicate "stop," and holding the arms outstretched to mean "so big."
XXY males frequently have trouble nding the right word to describe an object or a situa- tion. Parents and teachers can help them build vocabulary through a variety of techniques. One way is to provide them with synonyms, such as pointing out that a car is also called an automobile. Another important teaching tool is categorizing-showing the child that an item belongs to a larger class of items. With this technique, a child could be told that cars, buses, trucks, and bicycles are all vehicles, machines that carry people and things from place to place.
Because XXY boys have diculty expressing themselves, they may do poorly on essay-style test questions. Multiple choice questions will give teachers a better idea of what an XXY child has learned-and prove less stressful for him as well. Similarly, rather than asking an open- ended question, parents and teachers may wish to present alternatives. Instead of asking "What would you 'like to do now?" they may wish to o er a choice: "Would you rather work on your spelling or work on your math?"
Parents and teachers can help XXY boys develop the ability to express themselves through solicited dialogue engaging them in conversation through a series of questions. e same First of all, I spent a lot of time completing my thesis. erefore, I would like to dedicate my thesis to myself. Secondly, my parents provided me many ideas on this particular topic and tried to let me work on my thesis as comfortably as possible. us, I dedicate my thesis to my parents. Next, my teacher, Mi-Ran Lee has advised me on my writing and read this long thesis just for me to improve my skills. ere- fore, I dedicate my thesis to Miss Lee. (Or, maybe in the near future, Mrs. Lee!) Most importantly, there are numerous professionals that provided me the information I needed to write my thesis. I also dedicate my thesis to all of them. Everyone thanks a lot.
technique can be used to get the child to develop his narrative (storytelling) abilities. For example, a parent might begin by asking a child what he did at recess that day, and by follow- ing up with questions that get the child to talk about his activities: "Did you go down the slide? Were you afraid when you climbed all the way to the top of the ladder? And then what? Did you go on the seesaw? Who sat on the other end?"
Parents can also help XXY boys develop their expressive language abilities simply by provid- ing good examples. rough a technique known as modeling, they can help organize their children's thoughts and provide them with examples of how to express oneself. For instance, if a younger child indicated that he wanted a toy re engine by pointing at it and grunting, the parent could hand it to him while saying "Here you are. is is a re engine." Similarly, if an older child asked "Are we going to put the stu in the thing?” the parent might reply "Yes, we're going to put the oranges in the shopping cart."
Research indicates that XXY boys may do poorly in an open classroom situation and seem to prefer a structured, tightly organized environment centered around familiar routines. First, teachers can reduce distraction by placing them in front row seats. Teachers also should present information slowly and repeat key points several times, if necessary. XXY boys should not be given tasks that have many small steps. Rather, each step should be presented individu- ally. On completion, the child may then be asked to work on the next item in the series.
As mentioned above, XXY boys may withdraw from material they nd dicult and retreat into day dreaming. A teacher or parent should gently regain the child's attention and help him to focus again on the task at hand. Similarly, XXY boys may have diculty putting one task aside and beginning another one. Again, the parent or teacher should gently shi the child's attention, by saying something like "Drawing time is over. Let's put away the crayons and take out the math book."5
Second, therapeutic options are also available to XXY males. A variety of therapists, includ- ing physical, occupational, behavioral, speech, mental health, and family therapists, can o en help reduce or eliminate some of the symptoms of the XXY condition like poor muscle tone, speech and language problems, or low self-con dence.6 16 분당분원 - 손승연
ird, medical treatments can aid XXY males in curing the XXY condition. Testosterone replacement therapy (TRT) can greatly help them get their testosterone levels into normal range. Having a more normal testosterone level can lead to the development of bigger muscles ∙deeper voice∙ more facial and body hair,5 and improvement of concentration ∙ mood ∙ self esteem ∙ energy ∙ sex drive ∙ strength.9 It is recommended to start TRT when a boy reaches puberty. Some XXY males can also bene t from fertility treatment to help them father children.6 Surgery, when necessary, can reduce breast size.5
Albinism
Albinism (or in other words, called achromia, achromasia, or achromatosis) is a form of pigmentary congenital disorder, characterized by a partial or total lack of melanin pigment in the eyes, skin, hair, and ears. e condition is known to a ect mammals, sh, birds, reptiles and amphibians. It is di erent from leucism, where all integumental pigment is absent at least in patches but the eyes have their usual color.
e word “Albinism” derived from Latin word “albus,” meaning white. While the most common term for an organism a ected by albinism is "albino" (noun and adjective), the word is sometimes used in derogatory ways towards people. So, more neutral terms are "albinistic" (adjective) and "person with albinism" (noun). Additional clinical adjectives sometimes used to refer to animals are "albinoid" and "albinic”.13
Albinism is classi ed into several categories: oculocutaneous albinism (OCA) types 1, 2, 3, and 4; ocular albinism (OA). Moreover, albinism is characterized in Chediak-Higashi Syndrome (CHS), in Hermansky-Pudlak Syndrome (HPS), and in Griscelli Syndrome (GS).
e frequency of albinism di ers according to the types. OCA type 1 occurs in 1 per 40,000 populations, OCA type 2 in 1 per 15,000 populations, OCA type 3 is unknown, OCA type 4 is rare except in Japan, where 24% of individuals with OCA have this form, OA occurs in 1 per 50,000 population, CHS is extremely rare, HPS is rare except in Puerto Rico, where 1 out of 1800 population has HPS, and nally GS is extremely rare.
12 Jonathan Kantor. “Skin - abnormally dark or light.” Medline Plus. 29 October 2009. < http://www.nlm.nih.gov/medlineplus/ency/article/003242.htm > 13 Wikipedia. “Albinism.” Wikipedia. Date Unknown.
Melanin and Skin
Normal skin contains cells called melanocytes. ese cells produce melanin, the substance that gives skin its color.
Skin with too much melanin is called hyperpigmented skin. Skin with too little melanin is called hypopigmented skin.Pale skin areas are due to too little melanin or underactive melano- cytes. Darker areas on skin, or an area that tans more easily, are due to more melanin or overactive melanocytes.
Bronzing of the skin may sometimes be mistaken for a suntan. is skin discoloration o en develops slowly, starting at the elbows, knuckles, and knees and spreading from there. Bronz- ing may also be seen on the soles of the feet and the palms of the hands. e bronze color can range from light to dark (in fair-skinned people) with the degree of darkness due to the under- lying cause.12
14 Dr. Raymond E. Boissy; Dr. James J. Nordlund. "Albinism". eMedicine. 29 June 2007. < http://emedicine.medscape.com/article/1068184-overview > 18 분당분원 - 손승연
Cause
Albinism is hereditary; it is not an infectious disease and cannot be transmitted through contact, blood transfusions, or other vectors. Most forms of albinism are the result of the biologi- cal inheritance of recessive genes passed from both parents, though some rare forms are inher- ited from only one parent. ose genes prevent the body from making the usual amounts of the pigment melanin. Also, there are other genetic mutations which are proven to be associated with albinism. All alterations, however, lead to changes in melanin production in the body.13
First, OCA type 1 results from mutations in the tyrosinase gene, which maps to band 11q14-2 and is inherited as an autosomal (autosomes are the chromosomes except sex chro- mosomes) recessive trait. e enzyme called tyrosinase gene initiates the synthesis of melanin using the substrate tyrosine. Speci cally, tyrosinase hydroxylates tyrosine to dihydroxypheny- lalanine (DOPA) and subsequently dehydroxylates DOPA to DOPA-oxidase. More than 70 mutations have been identi ed in tyrosinase that results in the dysfunction or lack of synthesis of this enzyme. Most patients with OCA type 1 have compound heterozygosity for mutations in the tyrosinase gene.
Second, OCA type 2 results from mutation in the P gene, which maps to band 15q11-13 and is inherited as an autosomal recessive trait. e P gene encodes a 110-kd protein with 12 putative transmembrane domains localized to the limiting membrane of the pigment granule (i.e. melanosome). e function of the P protein in melanin synthesis has yet to be determined. ird, OCA type 3 results from mutation in the tyrosinase-related protein-1 (Tyrp1) gene, which maps to band 9p23 and is inherited as an autosomal recessive trait. e Tyrp1 gene encodes a protein that has been shown to have a dihydroxyindole carboxylic acid (DHICA) oxidase activity in the murine system. DHICA oxidase is a catalytic step downstream from tyrosinase in the biosynthesis of melanin from tyrosine. e function of Tyrp1 in human melanogenesis has yet to be con rmed.
Fourth, OCA type 4 results from mutations in the membrane-associated transporter protein (MATP) gene, which maps to band 5p13.3 and is inherited as an autosomal recessive trait. e MATP gene encodes a 58-kd protein with 12 predicted transmembrane domains. e function of MATP in melanogenesis is presently unknown. Fi h, OA results from mutation in a gene on the X chromosome, which maps to band Xp22.3- 22.2 and is inherited as an X-linked recessive trait. e function of the OA gene product is unknown.
Sixth, CHS results from mutation in the LYST gene, which maps to band 1q42-43 and is inherited as an autosomal recessive trait. e LYST gene encodes a large 429-kd protein that putatively functions in the translocation of material from the Golgi apparatus to target sites in a ected cells. As a result, the synthesis of melanosomes by the melanocyte, of delta granules by the platelet, and of lysosomes by some of the leukocytes (i.e. neutrophils and natural killer lymphocytes) is impaired.
Seventh, HPS is inherited as an autosomal recessive trait and exists with loci heterogeneity. e initial form of HPS identi ed, termed HPS type 1 (HPS1), results from a gene that maps to band 10q23.1-23.3. e HPS gene encodes a 79-kd protein of unknown function. HPS type 2 (HPS2) results from mutations in a gene that encodes the beta subunit of the adaptin 3 complex (AP3). AP3 is involved in tracking speci c glycoproteins from the Golgi apparatus to target sites in a ected cells. Many patients with HPS have normal HPS1 and HPS2 genes/gene products, suggesting that additional genetic causes for other subsets of HPS exist. To date, 8 genetically distinct forms of HPS have been identi ed in the human population.
Eighth, GS is inherited as an autosomal recessive trait. Two primary genetic variants are known. One results from mutations in the RAB27A gene located at band 15q21 that encodes the GTP-binding protein Rab27a. e other results from mutations in the MYO5A gene located at band 15q21 that encodes the unconventional myosin motor protein myosin5a. In the melanocyte, these 2 gene products, along with a third bridging protein (i.e. melanophilin) form a complex that facilitates the translocation of melanosomes along microtubules in the dendrites of the melanocyte and their subsequent capture by actin laments at the dendritic tips.14
Diagnosis
e hair bulb tyrosinase assay has been used to di erentiate between OCA type 1 and the other forms of albinism. In this assay, scalp hair bulbs are gently plucked from the patient and 20 분당분원 - 손승연
placed in a 0.1% solution of L-dihydroxyphenylalanine (L-DOPA) for up to 4 hours. If the sample is from a patient with OCA type 1 with mutations a ecting the synthesis or catalytic function of tyrosinase, the hair bulbs remain white. In contrast, samples from all other forms of albinism turn dark during the incubation period.
For CHS, a con rmatory workup consists of analysis of a blood smear and the subsequent identi cation of neutrophils containing giant cytoplasmic granules. For HPS, a con rmatory workup consists of electron microscopy of platelets and the subsequent identi cation of the absence of dense bodies (delta granules) and bleeding time determination that demonstrates a prolonged duration. For GS, con rmatory workup consist of immunological function evalua- tion plus both CT and MRI for neurological abnormalities. ese workups for albinism are not routine clinical tests.14
Symptoms
e characteristics of hypopigmentation are apparent at birth. An increase in the pigmenta- tion of the skin and/or the hair may occur with age, especially in individuals who are mildly a ected. e symptoms are di erent according to their categories.
First, OCA type 1 primarily manifests with complete absence of pigment in the skin, the hair, and the eyes, and this category is termed OCA type 1A. However, some patients can present with moderate pigmentation in these tissues, which is termed OCA type 1B. Others have pigment in hair follicles of the cooler areas of the body, such as the arms and the legs, and this is termed OCA type 1TS. All forms of OCA type 1 also present with photophobia (light sensitivity), moderate-to-severe reduced visual acuity, and nystagmus (involuntary eye move- ments). e latter two ocular dysfunctions result from a misrouting of the optic bers from the retina to the visual cortex of the brain.
Second, OCA type 2 does not present with complete absence of pigment but rather mani- fests with a minimal-to-moderate amount of pigment remaining in the skin, the hair, and the eyes. Many patients with OCA type 2 can develop pigmented freckles, lentigines, and/or nevi with age. e ocular presentations are similar to those in OCA type 1. ird, OCA type 3 manifests with minimal pigment reduction in the skin, the hair, and the eyes. is form of albinism was previously referred to as Rufous albinism and possibly Brown albinism. To date, OCA type 3 has only been genetically con rmed in dark-skinned individu- als of African heritage. e reduction of cutaneous and ocular pigmentation may only be apparent in comparison with the complexion coloration of family members. e ocular presentations are similar to those in OCA type 1, but they are not as severe.
Fourth, OCA type 4 manifests with a phenotype resembling OCA type 2.14
Fi h, OA primarily a ects the eyes. is condition reduces the pigmentation of the iris (the colored part of the eye) and the retina (the light-sensitive tissue at the back of the eye). Because the pigmentation in the eye is essential for normal vision, OA is characterized by severely impaired visual acuity and problems with stereoscopic vision, which means combining vision from both eyes to perceive depth. Although the vision loss is permanent, it does not worsen over time. Other eye abnormalities associated with this condition include problems with optic nerves, nystagmus, photophobia, and strabismus (eyes that do not look in the same direction).
Unlike some other forms of albinism, OA does not signi cantly a ect the pigmentation of the skin and hair. People with this condition may have a somewhat lighter complexion than other members of their family, but these di erences are usually minor.
e most common form of ocular albinism is known as the Nettleship-Falls type or type 1. Other forms of ocular albinism are much rarer and may be associated with additional signs and symptoms, such as hearing loss.15
Sixth, CHS manifests with moderate-to-complete absence of pigment in the skin, the hair, and the eyes. e pigmentation of the hair in CHS generally has a distinct silvery, metallic sheen. e accelerated phase of CHS generally manifests by the rst decade of life. Respiratory tract infections can occur within a few days of birth. Recurrent infections and bleeding diath- esis increase with the age of the patient. Children with CHS manifest easy bruising, mucosal bleeding, epistaxis, petechiae, recurrent infections primarily involving the respiratory system, and neutropenia; and, occasionally, thrombocytopenia, hepatosplenomegaly, lymphadenopathy,
15 U.S National Library of Medicine. "Ocular Albinism." Genetics Home Reference. Reviewed July 2007.
and jaundice. Neurologic problems are variable in CHS and include a peripheral and cranial neuropathy, autonomic dysfunction, weakness and sensory de cits, loss of deep tendon reexes, clumsiness with a wide-based gait, seizures, and decreased motor nerve conduction velocities. Death usually occurs in the rst decade from infection, bleeding, or development of the accelerated phase.
Seventh, HPS manifests with a variable amount of depigmentation in the skin, the hair, and the eyes. Ophthalmic ndings vary. In HPS, the bleeding diathesis can occur within a few days of birth generally during circumcision. roughout life, patients with HPS experience mild- to-moderate bleeding events, including bruising, epistaxis, gingival bleeding, prolonged bleed- ing during menstruation or a er tooth extraction, postpartum hemorrhage, and bleeding colitis. e respiratory system is the primary organ system a ected. Restrictive lung disease usually progresses slowly for the rst few decades of life and then advances rapidly. e occur- rence and the extent of other organ system dysfunctions are variable.
Eighth, GS manifests with a mild form of albinism (ie, pale skin). Distinctive in GS is the presentation of silvery gray hair at birth. In GS, the immunode ciency or neurological defects can occur shortly a er birth. Most individuals with GS develop chronic infections resulting from severe immunode ciency that can be fatal within the rst decade of life. GS can also manifest with immunode ciency and neurologic defects.14
To summarize, some common eye conditions associated with albinism, regardless of the categories of albinism, include the followings.
Additionally, there are some misconceptions about the patients of albinism. First, while some of the very rare albinism disorders that are coupled with deafness and immunode ciency, like Chediak-Higashi Syndrome, appear to be linked with inbreeding, the vast majority of su erers of common albinism are not the product of such unions; the more usual albinism genes are wide- spread enough that they can easily produce albinistic o spring from parents who are not related.
Among the other common misconceptions is that albinistic individuals of a species are sterile, but they are in fact fully capable of reproducing. It is also thought by many that people with albinism live short life spans. is is not true in general, but may be a distorted view of a more reason- able fact that people with albinism have a higher risk of skin cancer if they do not use proper skin protection when in the sun. (Some very rare variants of albinism are lethal by adulthood or sooner, but they are so little-known by the general public that they are unlikely to have contributed to this belief.) It has also been misunderstood that a person or other animal with albinism will become blind halfway through life; this is incorrect. Not all albinos are photophobic, but some tend to be.13
Treatment
Albinism is a condition that cannot be "cured,” but small things can be done to improve the quality of life for those a ected. ose include surgical treatments, vision aids, and sun protec- tion. e extent and success rate of these measures depend on the type of albinism and severity of the symptoms; in particular, people with ocular albinism are likely to have normally- pigmented skin, and thus do not need to take special precautions against skin damage.
First, surgical treatments can be applied. For the most part, treatment of the eye conditions consists of visual rehabilitation. Surgery is possible on the ocular muscles to decrease nystag- mus, strabismus and common refractive errors like astigmatism. Strabismus surgery may improve the appearance of the eyes. Nystagmus-damping surgery can also be performed, to reduce the "shaking" of the eyes back and forth. e e ectiveness of all these procedures varies greatly and depends on individual circumstances. More importantly, since surgery will not restore a normal RPE or foveae, surgery will not provide ne binocular vision. In the case of esotropia (the "crossed eyes" form of strabismus), surgery may help vision by expanding the visual eld (the area that the eyes can see while looking at one point).
Second, visual aids can help the patients. Glasses and other vision aids, large-print materials and closed captioning, and bright but angled reading lights, can help individuals with albinism. Some albinistic people do well using bifocals (with a strong reading lens), prescription reading glasses, and/or hand-held devices such as magni ers or monoculars (a very simple telescope). Contact lenses may be colored to block light transmission through the iris. Some use bioptics, 24 분당분원 - 손승연
glasses which have small telescopes mounted on, in, or behind their regular lenses, so that they can look through either the regular lens or the telescope. Newer designs of bioptics use smaller light-weight lenses. Some US states allow the use of bioptic telescopes for driving motor vehicles. Although still disputed among the experts, many ophthalmologists recommend the use of glasses from early childhood onward to allow the eyes the best development possible, even though their vision cannot be corrected completely. Optometrists or ophthalmologists who are experienced in working with low vision patients can recommend various optical aids. Some low-vision clinics provide these aids on trial loan, with instruction in their use.
ird, the protection from sunlight can greatly help the patients, either. It is vital that people with albinism use sunscreen when exposed to sunlight to prevent premature skin aging or skin cancer. is poses a problem for those who cannot a ord sunscreen, especially in regions with high exposure to sunlight, as in Africa. Use of sunglasses and hats with wide brims can make the glare outside bearable. Other things that can help people with albinism are avoiding sudden changes of the lighting situation (e.g. switching the light on in complete dark- ness), using dimmable switches and adding tint to car windows or blinds to normal windows. Lights should be yellowish rather than white and not point towards the usual position of a person with albinism (like their seat at a table).13
Most therapy for CHS and GS is symptomatic in nature. Appropriate antibiotics should be administered to treat infections. Bone marrow transplantation can correct and improve hematologic and immunologic defects in persons with CHS and GS, respectively.
No therapy is e ective for the nonpigmentary disorders of HPS. If the bleeding diathesis is extreme, platelet and blood transfusions may be considered. If the granulomatous colitis or the pulmonary brosis becomes extreme, high-dose steroids may be considered.14
Lives of the patients
In physical terms, humans with albinism commonly have vision problems and need sun protection. But they also face social and cultural challenges (even threats) as the condition is o en a source of ridicule, discrimination, or even fear and violence. Cultures around the world have developed many beliefs regarding people with albinism. is folklore ranges from harm- less myth to dangerous superstitions that cost human lives.
In African countries such as Tanzania and Burundi, there has been an unprecedented rise in witchcra -related killings of albino people in recent years. is is because albino body parts are used in potions sold by witchdoctors. Numerous authenticated incidents have occurred in Africa during the 21st Century. For example, in Tanzania, in September 2009, three men were convicted of killing a 14 year old albino boy and severing his legs in order to sell them for witchcra purposes.
Other examples: In Zimbabwe, belief that sex with an albinistic woman will cure a man of HIV has led to rapes (and subsequent HIV infections). In Jamaica, the albinistic have long been degraded, and regarded as "cursed.” Severe discrimination almost always happens in less devel- oped countries where the general scienti c knowledge of such occurrences are not widespread and superstition takes hold. It is also more frequent in countries where the skin color varies from people with albinism the most likely because they are more easily di erentiated from the general population.
Portrayals of people with albinism in literature and lms have historically rarely been positive. is fact is sometimes referred to as the "evil albino" stereotype, or albino bias. While this stereotype is common, in recent years a few more positive roles have also been cast for mock-albino actors and occasionally genuinely albinistic ones.
A number of real people with albinism have become famous, including historical gures such as Emperor Seinei of Japan, and Oxford don William Archibald Spooner; actor/comedian Victor Varnado; musicians such as Johnny and Edgar Winter, Salif Keita, Winston "King Yellowman" Foster, Brother Ali, Goldie of Ghood Ent and Willie "Piano Red" Perryman; and fashion model Connie Chiu.
ere have also been some famed albino animals, including Migaloo, a Humpback Whale o the coast of Australia; Snowake, a gorilla from a zoo in Barcelona; Snowdrop, a Bristol Zoo penguin; a pink dolphin in Louisiana and the Sperm Whale Mocha Dick, the inspiration for Herman Melville's novel Moby-Dick. (For the photograph of a pink dolphin, see Table 5.) 26 분당분원 - 손승연
Conclusion
Klinefelter’s syndrome can permanently bother the patients because it is the matter of appearance and also reproduction. I believe that performing testosterone replacement therapy (TRT) along with the special treatments to improve their linguistic skills is the best way to treat it. Even though the magnitude of the physical symptoms of Klinefelter’s syndrome di ers in all patients, TRT will signi cantly help to build more masculine shape. Because the self-con dence of people substantially depends on their appearance, the patients who experi- enced progress from TRT will regain their con dence, thinking that they are not much di er- ent from normal males in outlook.
However, if people are not good at communicating with others, they will never take part in the real society successfully. Hence, they must get particular education to enhance their faculty of speech. If the patients discover that they have Klinefelter’s syndrome while they are students, they should get school teachers’ special management at rst. As mentioned in the educational treatment part of the body “Klinefelter’s Syndrome,” teachers can help their comprehension even with simple words and behaviors.
But the most important treatment for all the patients of various genetic disorders is educat- ing normal people. No matter how much the patients undergo the medical treatments, they’ll become useless if other people keep viewing them with curiosity, fear, and surprise. People should know that they are not dangerous or infectious; in fact, they are just di erent in their features. Especially, the girl with albinism, who is mentioned in introduction, even referred that a lot of people send her ‘stupid’ e-mails asking if she is evil, has magical power, is stupid, is mentally retarded, or is socially awkward. She answered it all no, and said the physical di er- ences between normal people and people with albinism do not matter.
e eyes of people will make the patients uncomfortable and distressed. In my opinion, treating them casually usually is the best to both the patients and ordinary people. ACE THESIS Science & World History
Reference
* The footnotes in “The List of Tables” are excluded 1. Diana Chambers. “Klinefelter syndrome.” Medline Plus. 29 October 2009. < http://www.nlm.nih.gov/medlineplus/ency/article/000382.htm> 2. Dr. Raymond E. Boissy; Dr. James J. Nordlund. "Albinism". eMedicine. 29 June 2007. < http://emedicine.medscape.com/article/1068184-overview> 3. Encyclopedia Britannica. “Klinefelter’s syndrome.” Daum. Date Unknown.