The GALE ENCYCLOPEDIA of Genetic Disorders The GALE ENCYCLOPEDIA of Genetic Disorders VOLUME M-Z APPENDIX GLOSSARY INDEX S TAC E Y L B L AC H F O R D, E D I TO R The GALE ENCYCLOPEDIA of GENETIC DISORDERS STAFF Stacey L Blachford, Associate Editor Christine B Jeryan, Managing Editor Melissa C McDade, Associate Editor Ellen Thackery, Associate Editor Mark Springer, Technical Training Specialist Andrea Lopeman, Programmer/Analyst Barbara Yarrow, Manager, Imaging and Multimedia Content Robyn Young, Project Manager, Imaging and Multimedia Content Randy Bassett, Imaging Supervisor Robert Duncan, Senior Imaging Specialist Pamela A Reed, Coordinator, Imaging and Multimedia Content Maria Franklin, Permissions Manager Ryan Thomason, Permissions Associate Lori Hines, Permissions Assistant Since this page cannot legibly accommodate all copyright notices, the acknowledgments constitute an extension of the copyright notice While every effort has been made to ensure the reliability of the 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authors and editors of this work have added value to the underlying factual material herein through one or more of the following: unique and original selection, coordination, expression, arrangement, and classification of the information Gale Group and design is a trademark used herein under license All rights to this publication will be vigorously defended Kenn Zorn, Product Manager Michelle DiMercurio, Senior Art Director Mary Beth Trimper, Manager, Composition and Electronic Prepress Evi Seoud, Assistant Manager, Composition Purchasing and Electronic Prepress Dorothy Maki, Manufacturing Manager Ronald D Montgomery, Manager, Data Capture Gwendolyn S Tucker, Project Administrator Beverly Jendrowski, Data Capture Specialist Indexing provided by: Synapse Illustrations created by: Argosy, West Newton, Massachusetts Electronic Illustrators Group, Morgan Hill, California Copyright © 2002 Gale Group 27500 Drake Road Farmington Hills, MI 48331-3535 All rights reserved including the right of reproduction in whole or in part in any form ISBN 0-7876-5612-7 (set) 0-7876-5613-5 (Vol 1) 0-7876-5614-3 (Vol 2) Printed in the United States of America 10 Library of Congress Cataloging-in-Publication Data The Gale encyclopedia of genetic disorders / Stacey L Blachford, associate editor p cm Includes bibliographical references and index Summary: Presents nearly four hundred articles describing genetic disorders, conditions, tests, and treatments, including high-profile diseases such as Alzheimer’s, breast cancer, and heart disease ISBN 0-7876-5612-7 (set : hardcover : alk.paper Genetic disorders—Encyclopedias, Juvenile [1 Genetic disorders—Encyclopedias Diseases—Encyclopedias.] I Blachford, Stacey RB155.5 G35 2001 616’.042’03—dc21 2001040100 M Machado-Joseph disease see Azorean disease I Macular degeneration— age-related Definition Macular degeneration age-related (AMD) is one of the most common causes of vision loss among adults over age 55 living in developed countries It is caused by the breakdown of the macula, a small spot located in the back of the eye The macula allows people to see objects directly in front of them (called central vision), as well as fine visual details People with AMD usually have blurred central vision, difficulty seeing details and colors, and they may notice distortion of straight lines Description In order to understand how the macula normally functions and how it is affected by AMD, it is important to first understand how the eye works The eye is made up of many different types of cells and tissues that all work together to send images from the environment to the brain, similar to the way a camera records images When light enters the eye, it passes through the lens and lands on the retina, which is a very thin tissue that lines the inside of the eye The retina is actually made up of 10 different layers of specialized cells, which allow the retina to function similarly to film in a camera, by recording images The macula is a small, yellow-pigmented area located at the back of the eye, in the central part of the retina The retina contains many specialized cells called photoreceptors that sense light coming into the eye and convert it into electrical messages that are then sent to the brain through the optic nerve This allows the brain to “see” the environment GALE ENCYCLOPEDIA OF GENETIC DISORDERS The retina contains two types of photoreceptor cells: rod cells and cone cells The rod cells are located primarily outside of the macula and they allow for peripheral (side) and night vision Most of the photoreceptor cells inside of the macula, however, are the cone cells, which are responsible for perceiving color and for viewing objects directly in front of the eye (central vision) If the macula is diseased, as in AMD, color vision and central vision are altered There are actually two different types of AMD: Dry AMD and Wet AMD Dry AMD Approximately 90% of individuals with AMD have dry AMD This condition is sometimes referred to as nonexudative, atrophic, or drusenoid macular degeneration In this form of AMD, some of the layers of retinal cells (called retinal pigment epithelium, or RPE cells) near the macula begin to degenerate, or breakdown These RPE cells normally help remove waste products from the cone and rod cells When the RPE cells are no longer able to provide this “clean-up” function, fatty deposits called drusen begin to accumulate, enlarge and increase in number underneath the macula The drusen formation can disrupt the cones and rods in the macula, causing them to degenerate or die (atrophy) This usually leads to central and color vision problems for people with dry AMD However, some people with drusen deposits have minimal or no vision loss, and although they may never develop AMD, they should have regular eye examinations to check for this possibility Dry AMD is sometimes called “nonexudative”, because even though fatty drusen deposits form in the eye, people not have leakage of blood or other fluid (often called exudate) in the eye In some cases, dry AMD symptoms remain stable or worsen slowly In addition, approximately 10% of people with dry AMD eventually develop wet AMD Wet AMD Around 10% of patients with AMD have wet AMD This form of AMD is also called subretinal neovascular691 Macular degeneration—age-related KEY TERMS Central vision—The ability to see objects located directly in front of the eye Central vision is necessary for reading and other activities that require people to focus on objects directly in front of them Choroid—A vascular membrane that covers the back of the eye between the retina and the sclera and serves to nourish the retina and absorb scattered light Drusen—Fatty deposits that can accumulate underneath the retina and macula, and sometimes lead to age-related macular degeneration (AMD) Drusen formation can disrupt the photoreceptor cells, which causes central and color vision problems for people with dry AMD Genetic heterogeneity—The occurrence of the same or similar disease, caused by different genes among different families Macula—A small spot located in the back of the eye that provides central vision and allows people to see colors and fine visual details Multifactorial inheritance—A type of inheritance pattern where many factors, both genetic and environmental, contribute to the cause Optic nerve—A bundle of nerve fibers that carries visual messages from the retina in the form of electrical signals to the brain Peripheral vision—The ability to see objects that are not located directly in front of the eye Peripheral vision allows people to see objects located on the side or edge of their field of vision Photoreceptors—Specialized cells lining the innermost layer of the eye that convert light into electrical messages so that the brain can perceive the environment There are two types of photoreceptor cells: rod cells and cone cells The rod cells allow for peripheral and night vision Cone cells are responsible for perceiving color and for central vision Retina—The light-sensitive layer of tissue in the back of the eye that receives and transmits visual signals to the brain through the optic nerve Visual acuity—The ability to distinguish details and shapes of objects 692 ization, choroidal neovascularization, exudative form or disciform degeneration Wet AMD is caused by leakage of fluid and the formation of abnormal blood vessels (called “neovascularization”) in a thin tissue layer of the eye called the choroid The choroid is located underneath the retina and the macula, and it normally supplies them with nutrients and oxygen When new, delicate blood vessels form, blood and fluid can leak underneath the macula, causing vision loss and distortion as the macula is pushed away from nearby retinal cells Eventually a scar (called a disciform scar) can develop underneath the macula, resulting in severe and irreversible vision loss Genetic profile AMD is considered to be a complex disorder, likely caused by a combination of genetic and environmental factors This type of disorder is caused by multifactorial inheritance, which means that many factors likely interact with one another and cause the condition to occur As implied by the words “age-related”, the aging process is one of the strongest risk factors for developing AMD A number of studies have suggested that genetic susceptibility also plays an important role in the development of AMD, and it has been estimated that the brothers and sisters of people with AMD are four times more likely to also develop AMD, compared to other individuals Genetic factors Determining the role that genetic factors play in the development of AMD is a complicated task for scientists Since AMD is not diagnosed until late in life, it is difficult to locate and study large numbers of affected people in the same family In addition, although AMD seems to run in families, there is no clear inheritance pattern (such as dominant or recessive) observed when examining families However, many studies have supported the observation that inheritance plays some role in the development of AMD One method scientists use to locate genes that may increase a person’s chance to develop multifactorial conditions like AMD is to study genes that cause similar conditions In 1997, this approach helped researchers identify changes (mutations) in the ATP-binding cassette transporter, retina-specific (ABCR) gene in people diagnosed with AMD The process began after genetic research identified changes in the ABCR gene among people with an autosomal recessive macular disease called Stargardt macular dystrophy This condition is phenotypically similar to AMD, which means that people with Stargardt macular dystrophy and AMD have similar symptoms, such as yellow deposits in the retina and decreased central vision GALE ENCYCLOPEDIA OF GENETIC DISORDERS In 1998, another genetic researcher reported a family in which a unique form of AMD was passed from one generation to the next Although most families with AMD who are studied not show an obvious inheritance pattern in their family tree, this particular family’s pedigree showed an apparently autosomal dominant form of AMD Autosomal dominant refers to a specific type of inheritance in which only one copy of a person’s gene pair (i.e one allele) needs to have a mutation in order for it to cause the disease An affected person with an autosomal dominant condition thus has one allele with a mutation and one allele that functions properly There is a 50% chance for this individual to pass on the allele with the mutation, and a 50% chance to pass on the working allele, to each of his or her children Genetic testing done on the family reported in 1998 showed that the dominant gene causing AMD in affected family members was likely located on chromosome 1q25-q31 Although the gene linked to AMD in this family and the ABCR gene are both on chromosome 1, they are located in different regions of the chromosome This indicates that there is genetic heterogeneity among different families with AMD, meaning that different genes can lead to the same or similar disease among different families It is also possible that although one particular gene may be the main cause of susceptibility for AMD, other genes and/or environmental factors may help alter the age of onset of symptoms or types of physical changes seen by examining the eye Some studies have shown that other medical conditions or certain physical characteristics may be associated with an increased risk for AMD Some of these include: • Heart disease • High blood pressure GALE ENCYCLOPEDIA OF GENETIC DISORDERS • Cataracts • Farsightedness • Light skin and eye color However, not all studies have found a strong relationship between these factors and AMD Further research is needed to decipher the role that both genetic and environmental factors play in the development of this complex condition Environmental factors Determining the role that environmental factors play in the development of AMD is an important goal for researchers Unlike genetic factors that cannot be controlled, people can often find motivation to change their behaviors if they are informed about environmental risk factors that may be within their control Unfortunately, identifying environmental factors that clearly increase (or decrease) the risk for AMD is a challenging task Several potential risk factors have been studied These include: • Smoking • High fat/high cholesterol diet • Ultraviolet (UV) exposure (sunlight) • Low levels of dietary antioxidant vitamins and minerals Although research has identified these possible risk factors, many of the studies have not consistently shown strong associations between these factors and the development of AMD This makes it difficult to know the true significance of any of these risk factors One exception, however, is the relationship between smoking and AMD As of 1999, at least seven studies consistently found that smoking is strongly associated with AMD This is one more important reason for people to avoid and/or quit smoking, especially if they have a family history of AMD Further research is needed to clarify the significance of the factors listed above so people may be informed about lifestyle changes that may help decrease their risk for AMD Demographics Among adults aged 55 and older, AMD is the leading cause of vision loss in developed countries The chance to develop AMD increases with age, and although it usually affects adults during their sixth and seventh decades of life, it has been seen in some people in their forties It is estimated that among people living in developed countries, approximately one in 2,000 are affected by AMD By age 75, approximately 30% of people have early or mild forms of AMD, and roughly 7% have an advanced form of AMD Since the number of people in the United States aged 65 years or older will likely dou693 Macular degeneration—age-related The ABCR gene maps to chromosome 1p22, and people who have Stargardt macular dystrophy have mutations in each of their two alleles (gene copies) However, the researchers who found mutations in the ABCR gene among people with AMD located only one allele with a mutation, which likely created an increased susceptibility to AMD They concluded that people with an ABCR gene mutation in one allele could have an increased chance to develop AMD during their lifetime if they also had inherited other susceptibility genes, and/or had contact with environmental risk factors Other scientists tried to repeat this type of genetic research among people with AMD in 1999, and were not able to confirm that the ABCR gene is a strong genetic risk factor for this condition However, it is possible that the differing research results may have been caused by different research methods, and further studies will be necessary to understand the importance of ABCR gene mutations in the development of susceptibility to AMD Macular degeneration—age-related upon whether a person has dry or wet AMD In addition, the degree of vision loss and physical symptoms that can be seen by an eye exam change over time For example, people with dry AMD usually develop vision loss very slowly over a period of many years Their vision may change very little from one year to the next, and they usually not lose central vision completely However, individuals with wet AMD usually have symptoms that worsen more quickly and they have a greater risk to develop severe central vision loss, sometimes in as little as a two-month period Since people diagnosed with dry AMD may go on to develop wet AMD, it is important for them to take note of any changes in their symptoms and to report them to their eye care specialist A retinal photograph showing macular degeneration (Custom Medical Stock Photo, Inc.) ble between 1999 and 2024, the number of people affected also should increase Although AMD occurs in both sexes, it is slightly more common in women The number of people affected with AMD is different in various parts of the world and it varies between different ethnic groups Some studies suggest that AMD is more common in Caucasians than in African Americans; however, other reports suggest the numbers of people affected in these two groups are similar Some studies of AMD among Japanese and other Asian ethnic groups have shown an increasing number of affected individuals Further studies are needed to examine how often AMD occurs in other ethnic groups as well Signs and symptoms During eye examinations, eye care specialists may notice physical changes in the retina and macula that make them suspect the diagnosis of AMD However, affected individuals may notice: • Decreased visual acuity (ability to see details) of both up-close and distant objects • Blurred central vision • Decreased color vision • Distorted view of lines and shapes • A blind spot in the visual field The majority of people with AMD maintain their peripheral vision The severity of symptoms depends 694 The physical symptoms of AMD eventually impact people emotionally One study published in 1998 reported that people with advanced stages of AMD feel they have a significantly decreased quality of life In addition, they may have a limited ability to perform basic daily activities due to poor vision, and as a result, they often suffer psychological distress Hopefully, improved treatment and management will eventually change this trend for affected individuals in the future Diagnosis Eye care specialists use a variety of tests and examination techniques to determine if a person has AMD Some of these include: • Acuity testing—Involves testing vision by determining a person’s ability to read letters or symbols of various sizes on an “eye chart” from a precise distance away with specific lighting present • Color testing—Assesses the ability of the cone cells to recognize colors by using special pictures made up of dots of colors that are arranged in specific patterns • Amsler grid testing—Involves the use of a grid printed on a piece of paper that helps determine the health of the macula, by allowing people to notice whether they have decreased central vision, distorted vision, or blind spots • Fluorescein angiography—Involves the use of a fluorescent dye, injected into the bloodstream, in order to look closely at the blood supply and blood vessels near the macula The dye allows the eye specialist to examine and photograph the retina and macula to check for signs of wet AMD (i.e abnormal blood vessel formation or blood leakage) As of 2001, there are no genetic tests readily available to help diagnose AMD Genetic research in the coming years will hopefully help scientists determine the genetic basis of AMD This could help diagnose people GALE ENCYCLOPEDIA OF GENETIC DISORDERS Treatment and management Treatment There is no universal treatment available to cure either wet or dry forms of AMD However, some people with wet AMD can benefit from laser photocoagulation therapy This treatment involves the use of light rays from a laser to destroy the abnormal blood vessels that form beneath the retina and macula and prevent further leakage of blood and fluid Previously lost vision cannot be restored with this treatment, and the laser can unfortunately damage healthy tissue as well, causing further loss of vision In April 2000, the FDA approved the use of a lightactivated drug called Visudyne to help treat people with wet AMD Visudyne is a medication that is injected into the bloodstream, and it specifically attaches to the abnormal blood vessels present under the macula in people with AMD When light rays from a laser land on the blood vessels, the Visudyne is activated and can destroy the abnormal vessels, while causing very little damage to nearby healthy tissues Although long term studies are needed to determine the safety and usefulness of this medication beyond two years, early reports find it an effective way to reduce further vision loss Researchers have been trying to identify useful treatments for dry AMD as well Laser photocoagulation treatments are not effective for dry AMD since people with this form not have abnormal blood or fluid leakage Although many drugs have been tested, most have not improved visual acuity However, one study published in October 2000, reported that people with dry AMD who received a medication called Iloprost over a six-month period noted improvements in visual acuity, daily living activities and overall quality of life Followup studies will be needed to determine how safe and useful this medication will be over time Management Although no treatments can cure AMD, a number of special devices can help people make the most of their remaining vision Some of these include: • Walking canes • Guide dogs • Audiotapes GALE ENCYCLOPEDIA OF GENETIC DISORDERS • Magnifying lenses • Telescopes • Specialized prisms • Large print books • Reading machines • Computer programs that talk or enlarge printed information People with AMD may also find it useful to meet with low-vision specialists who can help them adapt to new lifestyle changes that may assist with daily living Eye care specialists can help people locate low-vision specialists There are also a number of nationwide and international support groups available that provide education and support for individuals and families affected by AMD Prognosis People can live many years with AMD, although the physical symptoms and emotional side effects often change over time The vision problems caused by dry AMD typically worsen slowly over a period of years, and people often retain the ability to read However, for people who develop wet AMD, the chance to suddenly develop severe loss of central vision is much greater Regular monitoring of vision by people with AMD (using an Amsler grid) and by their eye care specialists, may allow for early treatment of leaky blood vessels, therefore reducing the chance for severe vision loss As physical symptoms worsen, people are more likely to suffer emotionally due to decreasing quality of life and independence However, many low-vision devices and various support groups can often provide much needed assistance to help maintain and/or improve quality of life Resources BOOKS D’Amato, Robert, and Joan Snyder Macular Degeneration: The Latest Scientific Discoveries and Treatments for Preserving Your Sight New York: Walker & Co., 2000 Solomon, Yale, and Jonathan D Solomon Overcoming Macular Degeneration: A Guide to Seeing Beyond the Clouds New York: Morrow/Avon, 2000 PERIODICALS Bressler, Neil M., and James P Gills “Age related macular degeneration.” British Medical Journal 321, no 7274 (December 2000): 1425–1427 Fong, Donald S “Age-Related Macular Degeneration: Update for Primary Care.” American Family Physician 61, no 10 (May 2000): 3035–3042 “Macular degeneration.” Harvard Women’s Health Watch 6, no (October 1998): 2–3 695 Macular degeneration—age-related with increased susceptibility before they have symptoms, so they may benefit from early diagnosis, management and/or treatment This knowledge may also allow people who are at a genetically increased risk for AMD to avoid environmental risk factors and thus preserve or prolong healthy vision Major histocompatibility complex “Researchers set sights on vision disease.” Harvard Health Letter 23, no.10 (August 1998):4–5 “Self-test for macular degeneration.” Consumer Reports on Health 12, no.12 (December 2000): ORGANIZATIONS AMD Alliance International PO Box 550385, Atlanta, GA 30355 (877) 263-7171 Ͻhttp://www.amdalliance.orgϾ American Macular Degeneration Foundation PO Box 515, Northampton, MA 01061-0515 (413) 268-7660 Ͻhttp://www.macular.orgϾ Foundation Fighting Blindness Executive Plaza 1, Suite 800, 11350 McCormick Rd., Hunt Valley, MD 21031 (888) 394-3937 Ͻhttp://www.blindness.orgϾ Macular Degeneration Foundation PO Box 9752, San Jose, CA 95157 (888) 633-3937 Ͻhttp://www.eyesight.orgϾ Retina International Ausstellungsstrasse 36, Zürich, CH-8005 Switzerland (ϩ41 444 10 77) Ͻhttp://www.retinainternational.orgϾ Pamela J Nutting, MS, CGC Madelung deformity see Leri-Weill dyschondrosteosis Maffuci disease see Chondrosarcoma I Major histocompatibility complex Definition In humans, the proteins coded by the genes of the major histocompatibility complex (MHC) include human leukocyte antigens (HLA), as well as other proteins HLA proteins are present on the surface of most of the body’s cells and are important in helping the immune system distinguish ‘self’ from ‘non-self’ Description The function and importance of MHC is best understood in the context of a basic understanding of the function of the immune system The immune system is responsible for distinguishing ‘self’ from ‘non-self’, primarily with the goal of eliminating foreign organisms and other invaders that can result in disease There are several levels of defense characterized by the various stages and types of immune response Natural immunity When a foreign organism enters the body, it is encountered by the components of the body’s natural 696 immunity Natural immunity is the non-specific first-line of defense carried out by phagocytes, natural killer cells, and components of the complement system Phagocytes are specialized white blood cells capable of engulfing and killing an organism Natural killer cells are also specialized white blood cells that respond to cancer cells and certain viral infections The complement system is a group of proteins called the class III MHC that attack antigens Antigens consist of any molecule capable of triggering an immune response Although this list is not exhaustive, antigens can be derived from toxins, protein, carbohydrates, DNA, or other molecules from viruses, bacteria, cellular parasites, or cancer cells Acquired immunity The natural immune response will hold an infection at bay as the next line of defense mobilizes through acquired, or specific immunity This specialized type of immunity is usually needed to eliminate an infection and is dependent on the role of the proteins of the major histocompatibility complex There are two types of acquired immunity Humoral immunity is important in fighting infections outside the body’s cells, such as those caused by bacteria and certain viruses Other types of viruses and parasites that invade the cells are better fought by cellular immunity The major players in acquired immunity are the antigen-presenting cells (APCs), B-cells, their secreted antibodies, and the T-cells Their functions are described in detail below Humoral immunity In humoral immunity, antigen-presenting cells, including some B-cells, engulf and break down foreign organisms Antigens from these foreign organisms are then brought to the outside surface of the antigen-presenting cells and presented in conjunction with class II MHC proteins The helper T-cells recognize the antigen presented in this way and release cytokines, proteins that signal B-cells to take further action B-cells are specialized white blood cells that mature in the bone marrow Through the process of maturation, each B-cell develops the ability to recognize and respond to a specific antigen Helper T-cells aid in stimulating the few B-cells that can recognize a particular foreign antigen B-cells that are stimulated in this way develop into plasma cells, which secrete antibodies specific to the recognized antigen Antibodies are proteins that are present in the circulation, as well as being bound to the surface of B-cells They can destroy the foreign organism from which the antigen came Destruction occurs either directly, or by ‘tagging’ the organism, which will then be more easily recognized and targeted by phagocytes and complement proteins Some of the stimulated B-cells go on to become memory GALE ENCYCLOPEDIA OF GENETIC DISORDERS Cellular immunity Another type of acquired immunity involves killer Tcells and is termed celluar immunity T-cells go through a process of maturation in the organ called the thymus, in which T-cells that recognize ‘self’ antigens are eliminated Each remaining T-cell has the ability to recognize a single, specific, ‘non-self’ antigen that the body may encounter Although the names are similar, killer T-cells are unlike the non-specific natural killer cells in that they are specific in their action Some viruses and parasites quickly invade the body’s cells, where they are ‘hidden’ from antibodies Small pieces of proteins from these invading viruses or parasites are presented on the surface of infected cells in conjunction with class I MHC proteins, which are present on the surface of most all of the body’s cells Killer T-cells can recognize antigen bound to class I MHC in this way, and they are prompted to release chemicals that act directly to kill the infected cell There is also a role for helper T-cells and antigen-presenting cells in cellular immunity Helper T-cells release cytokines, as in the humoral response, and the cytokines stimulate killer T-cells to multiply Antigen-presenting cells carry foreign antigen to places in the body where additional killer T-cells can be alerted and recruited The major histocompatibility complex clearly performs an important role in functioning of the immune system Related to this role in disease immunity, MHC is important in organ and tissue transplantation, as well as playing a role in susceptibility to certain diseases HLA typing can also provide important information in parentage, forensic, and anthropologic studies These various roles and the practical applications of HLA typing are discussed in greater detail below Genetic profile Present on chromosome 6, the major histocompatibility complex consists of more than 70 genes, classified into class I, II, and III MHC There are multiple alleles, or forms, of each HLA gene These alleles are expressed as proteins on the surface of various cells in a co-dominant manner This diversity is important in maintaining an effective system of specific immunity Altogether, the MHC genes span a region that is four million base pairs in length Although this is a large region, 99% of the time these closely-linked genes are transmitted to the next generation as a unit of MHC alleles on each chromosome This unit is called a haplotype Class I Class I MHC genes include HLA-A, HLA-B, and HLA-C Class I MHC are expressed on the surface of GALE ENCYCLOPEDIA OF GENETIC DISORDERS almost all cells They are important for displaying antigen from viruses or parasites to killer T-cells in cellular immunity Class I MHC is also particularly important in organ and tissue rejection following transplantation In addition to the portion of class I MHC coded by the genes on chromosome 6, each class I MHC protein also contains a small, non-variable protein component called beta-2 microglobulin coded by a gene on chromosome 15 Class I HLA genes are highly polymorphic, meaning there are multiple forms, or alleles, of each gene There are at least 57 HLAA alleles, 111 HLA-B alleles, and 34 HLA-C alleles Class II Class II MHC genes include HLA-DP, HLA-DQ, and HLA-DR Class II MHC are particularly important in humoral immunity They present foreign antigen to helper T-cells, which stimulate B-cells to elicit an antibody response Class II MHC is only present on antigen presenting cells, including phagocytes and B-cells Like class I MHC, there are hundreds of alleles that make up the class II HLA gene pool Class III Class III MHC genes include the complement system (i.e C2, C4a, C4b, Bf) Complement proteins help to activate and maintain the inflammatory process of an immune response Demographics There is significant variability of the frequencies of HLA alleles among ethnic groups This is reflected in anthropologic studies attempting to use HLA-types to determine patterns of migration and evolutionary relationships of peoples of various ethnicity Ethnic variation is also reflected in studies of HLA-associated diseases Generally speaking, populations that have been subject to significant patterns of migration and assimilation with other populations tend to have a more diverse HLA gene pool For example, it is unlikely that two unrelated individuals of African ancestry would have matched HLA types Conversely, populations that have been isolated due to geography, cultural practices, and other historical influences may display a less diverse pool of HLA types, making it more likely for two unrelated individuals to be HLA-matched Testing Organ and tissue transplantation There is a role for HLA typing of individuals in various settings Most commonly, HLA typing is used to establish if an organ or tissue donor is appropriately matched to the recipient for key HLA types, so as not to 697 Major histocompatibility complex cells, which are able to mount an even faster response if the antigen is encountered a second time Limb-girdle muscular dystrophy (LGMD), 1:668–673 , 669, 671 classification, 2:769 genetic profile, 2:770–772 signs and symptoms, 2:773 LIMK1 gene, 2:1196 Lindau, Arvid, 2:1173 Linkage analysis Bardet-Biedl syndrome, 1:137–139 Duchenne muscular dystrophy, 1:363 familial adenomatous polyposis, 1:410–411 genetic mapping, 1:457 indirect DNA testing, 1:476 Osler-Weber-Rendu syndrome, 2:852 Treacher Collins syndrome, 2:1141 Lipid metabolism carnitine palmitoyltransferase deficiency, 1:201–202 hyperlipoproteinemia, 1:582 mucolipidosis, 2:751 Lipofuscinosis, 1:140 Lipomas, 1:39 Lipopigments, 1:140 Lipoproteins, 1:6, 582 LIS1 gene lissencephaly, 1:675–676 Miller-Dieker syndrome, 2:744–746 Lissencephaly, 1:673–676 , 675 Miller-Dieker syndrome, 2:744–746 Walker-Warburg syndrome, 2:1187–1188 Lithium carbonate bipolar disorder type II, 1:161–162 nephrogenic diabetes insipidus, 2:794 Lithotripsy, cystinuria, 1:307 Little People of America, 1:20 Liver biopsy hemochromatosis, 1:519–520 liver cancer, 1:679 Liver cancer, 1:677–681 , 679 alcohol abuse and, 1:190 risk factors, 1:678 Liver disease Alagille syndrome, 1:42 alpha-1 antitrypsin, 1:62–63 asplenia, 1:114 color blindness, 1:257–258 hemochromatosis, 1:519–520 Wilson disease, 2:1198–1201 Liver function test, 1:52 Liver transplantation, 1:680, 2:849–850 Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), 2:844, 846 Long-chain acyl-CoA dehydrogenase (LCAD), 2:843 GALE ENCYCLOPEDIA OF GENETIC DISORDERS Long-chain fatty acids, 1:202 Long-QT syndrome (LQTS), 1:681–686 drug contraindications, 1:684 Jervell and Lange-Nielsen syndrome, 1:618–620 Longitudinal study, alcoholism, 1:49 Lorenzo’s oil, 1:37 Loss of heterozygosity, 1:541 Lou Gehrig’s disease, 1:79–82 , 80–81 Low density lipoproteins (LDL), 1:6, 2:1109 Lowe syndrome, 1:687–690 , 689 LQTS See Long-QT syndrome (LQTS) Lung transplantation, 1:300–301 Lungs asplenia and defects in, 1:114 chronic lung disease, 1:62 cystic fibrosis, 1:297 Fryns syndrome, 1:443 Lupus erythematosus hair loss, 1:505 Raynaud disease, 2:979 Luteinizing hormone Kallman syndrome, 1:628–629 Klinefelter syndrome, 1:637–638 LWD (Leri-Weill dyschonodrosteosis), 1:658–660 Lymphedema distichiasis, 1:581 Lymphoma, 1:189 Lynch syndrome See Muir-Torre syndrome Lysosomal storage disease galactosialodosis, 2:807–808 GM1-gangliosidosis, 1:487–490 mannosidosis, 2:704–706 mucolipidosis, 2:751 neuraminidase deficiency, 2:803 Lysosome, Batten disease, 1:140 LYST gene, 1:226 IM Machado, William, 1:135 Machado-Joseph disease, 1:135–137 Macroglossia, 1:147–149 Macula pigmentation neuroaminidase deficiency, 2:807–811 Niemann-Pick disease, 2:814–815 Macular corneal dystrophy, 1:275–277 Macular degeneration age-related, 2:691–695 , 694 color blindness, 1:258 Mad cow disease, 2:949–952 Madelung’s deformity, 1:659 1331 Index LCA (Leber congenital amaurosis), 1:649–652 L1CAM gene, 2:1214–1218 LCHAD (Long-chain 3-hydroxyacylCoA dehydrogenase), 2:844, 846 LDL (Low density lipoproteins), 1:6, 2:1109 Leber, Theodore, 1:649–650 Leber congenital amaurosis (LCA), 1:649–652 Lebers hereditary optic atrophy, 1:652–655 Lee, Pearl, 1:149 Leigh syndrome, 1:655–658 Leri-Weill dyschonodrosteosis (LWD), 1:658–660 Lejeune, Jerome, 1:290 Leloir, L F., 1:447 Lemli, Luc, 2:1065 LEOPARD syndrome multiple lentigenes syndrome, 2:768 vs Noonan syndrome, 2:821 Leprosy, thalidomide therapy, 2:1128 Leptomeningeal angioma, 2:1103–1105 Leroy, Jules, 2:750–751 Leroy disease, 2:750–753, 2: 803 Lesch, Michael, 1:660 Lesch-Nyhan syndrome, 1:464, 1:660–662 , 661 Leukemia classification, 1:189 color blindness, 1:258 Li-Fraumeni syndrome, 1:665–666 sideroblastic X-linked anemia, 1:88 Leukocoria, 2:992–993 Leukodystrophy, 1:662–664 adrenoleukodystrophy, 1:37 infantile refsum disease, 1:603–605 Zellweger syndrome, 2:1225–1227 Leventhal, M L., 2:935 Lewy body dementia, 1:316, 318 LFS See Li-Fraumeni syndrome LGMD See Limb-girdle muscular dystrophy LGS (Langer-Giedion syndrome), 1:236, 1:645–646 Li-Fraumeni syndrome (LFS), 1:665–668 , 667 defined, 1:193 stomach cancer, 2:1099 Lichen planopilaris, 1:505 Lifetime risk, cancer demographics, 1:190 Light sensitivity, 1:21–23 LIM homeobox transcription factor 1beta, 2:789 Index Maffuci disease, 1:227–228 Magenis, Ellen, 2:1068 Magnani, M., 1:448 Magnetic resonance imaging (MRI) adrenoleukodystrophy, 1:37 Aicardi syndrome, 1:40 alkaptonuria, 1:59 ankylosing spondylitis, 1:94, 96 Arnold-Chiari malformation, 1:103 breast cancer, 1:175 cancer screening, 1:194 congenital heart defects, 1:268–269 conjoined twins, 1:274 epilepsy, 1:395 hemochromatosis, 1:519 Moyamoya, 2:749 Pelizaeus-Merzbacher disease, 2:900 spinocerebellar ataxia, 2:1086 Majewski syndrome, 2:1044–1046 Major histocompatibility complex (MHC), 2:696–700 Male pattern hair loss, 1:504–508 Male Turner syndrome See Noonan syndrome Malignant hyperthermia (MH), 2:700–704 central core disease, 1:212 Freeman-Sheldon syndrome, 1:438 muscular dystrophy, 2:775 pharmacogenetics, 2:917–918 Schwartz-Jampel syndrome, 2:1031 Malrotation, asplenia, 1:112 MANB/MANB1 gene, 2:705–706 Manic-depressive See Bipolar disorder Mannosidosis, 2:704–706 Marchiafava-Micheli syndrome, 2:888–890 Marden-Walker syndrome, 2:1030 Marfan syndrome, 2:706–712 vs Cohen syndrome, 1:255 congenital heart defects, 1:268 homocystinuria, 1:564 Shprintzen-Goldberg craniosynostosis syndrome, 2:1046 Marfanoid habitus, 1:105 Marie, Pierre, 1:29 Marker X syndrome See Fragile X syndrome Maroteaux-Lamy syndrome, 2:756 Marshall, D., 2:712–713 Marshall-Smith syndrome (MSS), 2:714–716 Marshall syndrome, 2:712–714 Stickler syndrome, 2:1094–1095 Weissenbacher-Zweymuller syndrome, 2:1192 Martin-Bell syndrome See Fragile X syndrome 1332 Mason, H H., 1:447 Masseter spasm, 2:701 Maternal age chromosomal abnormalities, 1:237–238 Down syndrome, 1:348–349, 351 Patau syndrome, 2:891 Maternal serum alpha-fetoprotein test Down syndrome, 1:351 trisomy 18 diagnosis, 2:1147 Maturity-onset diabetes of the young classification, 1:328 diagnosis, 1:335 genetics, 1:332 signs and symptoms, 1:334 May-Hegglin anomaly, 2:1037 MCAD (Medium chain acyl-CoA dehydrogenase deficiency), 2:717–720, 2: 843, 845–846 McCune-Albright syndrome, 1:30, 2:720–722 , 722 McKusick-Kaufmann syndrome, 1:138–139, 2:722–724 , 724 McKusick type dysplasia, 2:733–734 MCM (Methylmalonicaciduria due to methylmalonic CoA mutase deficiency), 2:738–740, 2: 844 MDS See Miller-Dieker syndrome Mean corpuscular volume (MCV), 1:52 Meckel, Johann F., 2:725, 727 Meckel-Gruber syndrome (MGS), 2:726–729 Meckel’s diverticulum, 1:279, 281, 2:724–726 , 726 Meconium ileus, cystic fibrosis, 1:296 Medium chain acyl-CoA dehydrogenase deficiency (MCAD), 2:717–720, 2: 843, 845–846 Medullary thyroid carcinoma, 2:764–765 Medulloblastoma, 1:194 Meesman’s corneal dystrophy, 1:275–277 MEFV gene, 1:414–416 Meiosis chromosome structure, 1:236 trisomy 18, 2:1145 Melanin albinism, 1:44 alkaptonuria, 1:57 Hermansky-Pudlak syndrome, 1:549–551 Melanoma, 1:189 MELAS syndrome, 1:331, 332 Melnick, M., 1:171 Melnick-Fraser syndrome, 1:170–173 , 172 Melnick-Needles syndrome, 2:863–864 MEN-1 (Multiple endocrine neoplasia-1), 1:30–32, 1:763–767 MEN-2 (Multiple endocrine neoplasia-2), 1:478, 763–767, 836 MEN-3 (Multiple endocrine neoplasia-3), 2:763–767 MEN1 gene, 2:765–766 Mendel, Gregor, 1:55, 57, 342, 455, 606 Mendelian inheritance, 1:606–609 autosomal dominant, 1:606–607 autosomal recessive, 1:607 autosomal semi-dominant, 1:607 sex-linked, 1:607–609 Meningomyelocele See Spina bifida Menkes syndrome, 2:729–732 Mental status examination (MSE), 1:319–320 Mercaptopropionylglycine, cystinuria, 1:307 Meromelia, 1:70 Merrick, Joseph (John), 2:961 Merzbacher, L., 2:899 Mesobrachyphalangy, 2:825–826 Mesomelia, Leri-Weill dyschonodrosteosis, 1:659 Messenger RNA (mRNA), 1:456, 2:1004–1005 Metabolic myopathies, 1:203 Metabolism cholesterol, 1:557, 2:1065–1068, 1109–1112 copper, 2:731–732, 1198–1201 inborn error of (See Inborn error of metabolism) lipid, 1:201–202, 582, 2:751 nitrogen, 2:847–850 Metachromatic leukodystrophy, 1:663 Metafemales, sex chromosome aneuploidy, 1:235 Metaphyseal acroscyphodysplasia, 2:735 Metaphyseal anadysplasia, 2:733–734 Metaphyseal dysplasia, 2:733–735 Metarhodopsin II, 2:1000 Metastatic liver cancer, 1:677 Methionine homocystinuria, 1:562–565 prion diseases, 2:950–952 3-Methylcrotonglycemia, 2:844 Methylene H4-folate molecule, homocystinuria, 1:564–565 Methylmalonic acidemia (MMA), 2:735–737 pancreatic beta cell agenesis, 2:875–876 symptoms, 2:844 GALE ENCYCLOPEDIA OF GENETIC DISORDERS Mitral valve prolapse Beals syndrome, 1:142 Fabry disease, 1:402 Marfan syndrome, 2:708 Stickler syndrome, 2:1096 Mixed type hearing loss, 1:536 MKKS gene, 1:137–139 MKS gene, 2:723–724 MMA See Methylmalonic acidemia MNK gene, 2:729–731 Moderate asthma, 1:120 Möebius syndrome, 2:747–748 Molar pregnancy, 2:1229 Mondini malformation, 2:904–905 Monoamine oxidase B, Parkinson disease, 2:886–887 Monoamine oxidase inhibitors depression management, 1:327 panic disorder, 2:883 Monozygous twins, 1:7–8 Morgan, Thomas Hunt, 1:342, 456–457 Morning glory syndrome, 1:255–256 Morquio syndrome, 2:756 Mosaic trisomy 18, 2:1146 Mosaicism fragile X syndrome, 1:431 germ line (See Germ line mosaicism) gonadal, 2:1131–1132 pedigree analysis, 1:611 Proteus syndrome, 2:961 thanatophoric dysplasia, 2:1131 Turner syndrome, 2:1155 Motilin receptors, pyloric stenosis, 2:968 Motor/vocal tics, 2:1137 Moyamoya, 2:748–750 MPS See Mucopolysaccharidoses MPTP, Parkinson disease, 2:885 MRI See Magnetic resonance imaging MRP6 gene, 2:966–967 MSH and genes, 1:478 MSS (Marshall-Smith syndrome), 2:714–716 MSX1 gene, 1:245 MSX2 gene, 1:205, 287 MTP (Microsomal triglyceride transfer protein), 1:5 Mucolipidosis (ML), 2:750–753, 2: 803 Mucopolysaccharidoses (MPS), 2:753–757 Hunter syndrome, 1:567–569 Hurler syndrome, 1:572–575 Schwartz-Jampel syndrome, 2:1030 Muenke syndrome, 1:287 Muir-Torre syndrome, 2:757–760 , 759 Multi-infarct dementia, 1:316–318 GALE ENCYCLOPEDIA OF GENETIC DISORDERS Multi-Torre syndrome, 1:531–533 Multifactorial inheritance, 2:760–763 autism, 1:130 celiac disease, 1:208 cleft lip and palate, 1:241 encephalocele, 1:387 hydrops fetalis, 1:580–581 macular degeneration age-related, 2:692–695 patent ductus arteriosus, 2:895–896 zygote formation, 2:1229 Multifocal breast cancer, 1:194 Multigenerational studies, alcoholism genetics, 1:48–49 Multiorgan CPT-II deficiency, 1:203 Multiple births, cerebral palsy, 1:214–215 Multiple endocrine neoplasia-1 (MEN1), 1:30–32, 2:763–767 Multiple endocrine neoplasia-2 (MEN2), 1:478, 2:836 Multiple endocrine neoplasia-3 (MEN3), 2:763–767 Multiple endocrine neoplasias, 2:763–767 , 765 Multiple lentigenes syndrome, 2:768–769, 2: 821 Multiple sclerosis color blindness, 1:258 Lebers hereditary optic atrophy, 1:654 Muscle biopsy Duchenne muscular dystrophy, 1:362–363 muscular dystrophy, 2:774 Muscle CPT deficiency, 1:203 Muscular atrophy, 1:6 Muscular dystrophy, 2:769–776 , 775 vs acid maltase deficiency, 1:23 Duchenne muscular dystrophy, 1:359–363 Emery-Dreifuss muscular dystrophy (See Emery-Dreifuss muscular dystrophy) vs Engelmann disease, 1:390 FSH muscular dystrophy, 1:444–446 genetic counseling, 1:470 vs leukodystrophy, 1:664 limb-girdle muscular dystrophy, 1:668–673 Walker-Warburg syndrome, 2:1187–1188 Mut0 gene, 2:738–740 Muton, gene structure, 1:455 Myalgia, familial Mediterranean fever, 1:416 Myasthenia gravis, 2:776–779 Myelin adrenoleukodystrophy, 1:37 Krabbe disease, 1:641–643 1333 Index Methylmalonicaciduria due to methylmalonic CoA mutase deficiency, 2:738–740, 2: 844 Metopic craniosynostosis, 1:288 Metronidazole, methylmalonicaciduria, 2:740 MH See Malignant hyperthermia MHC (Major histocompatibility complex), 2:696–700 MHS genes, 2:702–703 Michigan Alcoholism Screening Test, 1:52 Microarray, alcoholism, 1:49–50 Microcephaly accutane embryopathy, 1:12 Cornelia de Lange syndrome, 1:279 Dubowitz syndrome, 1:358 Neu-Laxova syndrome, 2:797 Paine syndrome, 2:871–872 Smith-Lemli-Opitz syndrome, 2:1065–1068 Micrognathia Cornelia de Lange syndrome, 1:279 Pierre-Robin sequence, 2:922–925 Micromelia achondrogenesis, 1:15 thanatophoric dysplasia, 2:1130 Microphthalmia with linear skin defects, 2:741–743 Aicardi syndrome, 1:39 Goltz syndrome, 1:494 Microsomal triglyceride transfer protein (MTP), 1:5 Mid-trimester amniocentesis, 1:77–78 Miescher, Johann, 1:342 Mild androgen insensitivity, 1:83–86 Mild persistent asthma, 1:120 Miller, J., 2:744 Miller-Dieker syndrome (MDS), 1:236, 675–676, 2:744–746 Milwaukee brace, scoliosis, 2:1036 Mineral supplementation, cystinosis, 1:304 Minoxidil, hair loss treatment, 1:507–508 Mirhosseini-Holms-Walton syndrome, 1:252–255 Miscarriage, 1:13, 78 Misoprostol, Möebius syndrome, 2:747–748 Mitochondrial DNA diabetes mellitus, 1:335 hereditary hearing loss and deafness, 1:537–538 inheritance, 1:606 inheritance characteristics, 1:610 Lebers hereditary optic atrophy, 1:653–655 Leigh syndrome, 1:656 Index Myelin protein zero gene, 1:219–220 Myelodysplasia, 1:87 Myelogenous leukemia, 1:419 MYO5A, 1:499 Myoblast transfer, muscular dystrophy, 2:776 Myopathies, 1:25, 203 Myopia, 2:780–784 , 783 Bardet-Biedl syndrome, 1:138 Beals syndrome, 1:142–143 choroideremia, 1:230 Cohen syndrome, 1:254 Cornelia de Lange syndrome, 1:280 homocystinuria, 1:563 Marfan syndrome, 2:708 Marshall syndrome, 2:713 Schwartz-Jampel syndrome, 2:1029–1031 Myosin heavy chain gene, 2:1038 Myosin VA protein, Griscelli syndrome, 1:499 Myotonia myotonic dystrophy, 2:786–787 Rieger syndrome, 2:1002 Myotonic dystrophy (DM), 2:785–788 , 786–787 classification, 2:770 genetic profile, 2:772 hydrops fetalis, 1:581 Rieger syndrome, 2:1002 Schwartz-Jampel syndrome diagnosis, 2:1030 signs and symptoms, 2:773 Myotonic dystrophy protein kinase, 2:785–788 Myotrophin, amyotrophic lateral sclerosis, 1:82 IN N-Acetylaspartic acid, Canavan disease, 1:186 Nail-patella syndrome, 2:789–791 , 791 Naltrexone, 1:49, 53 Narcolepsy, 2:791–793 , 793 Nasolacrimal duct fistula, 1:280 National Cholesterol Education Program, 1:583 National Library of Medicine-Breath of Life Exhibit, 1:119 Natito-Oyanagi disease, 1:321–323 Natural immunity, major histocompatibility complex, 2:696 Natural selection, gene mutation, 1:459 NBS1 gene, 2:817 NBS (Nijmegen breakage syndrome), 2:816–818 1334 ND (Norrie disease), 2:822–824 NDI (Nephrogenic diabetes insipidus), 2:793–796 NDP protein, Norrie disease, 2:822–823 Negative pressure ventilation, spinal muscular atrophy, 2:1083 NEMO gene, 1:600–603 Neonatal diabetes mellitus, 2:876 Neonatal hypoglycemia, 1:146, 148 Neonatal pyruvate carboxylase deficiency, 2:970–972 Nephrogenic diabetes insipidus (NDI), 2:793–796 Nerve growth factor, Alzheimer disease, 1:69 NEU1 gene, 2:802–804 Neu-Laxova syndrome, 2:797–799 Neural crest cells, neurofibromatosis, 2:811–813 Neural migration disorders, 1:673–676 Neural tube defects, 2:800–802 , 801 anencephaly, 1:89–90 encephalocele, 1:387–389 multifactorial inheritance, 2:761–762 Neuraminidase deficiency, 2:802–807 galactosialodosis, 2:810 mucolipidosis, 2:751 nomenclature, 2:802–803 Neuraminidase deficiency with beta galactosidase deficiency, 2:807–811 Neurofibromatosis (NF), 2:811–813 , 812 Noonan syndrome, 2:818–821 pedigree analysis, 2:897 Neuroimaging Alzheimer disease, 1:65, 68 Asperger syndrome, 1:110–111 demential diagnosis, 1:320 Leigh syndrome, 1:656 panic disorder, 2:882–883 Neurological examination, dementia, 1:320 Neuromuscular conditions, 1:6 Neuronal ceroid lipofuscinoses, 1:140 Neuropathies adrenomyeloneuropathy, 1:36–37 hereditary sensory and autonomic, 1:412 with liability to pressure palsies, 1:219 Nevi, 1:166–167 Nevoid basal cell carcinoma syndrome, 1:494 Newborn screening chromosome analysis, 1:479–480 congenital adrenal hyperplasia, 1:265 cystic fibrosis, 1:299 galactokinase deficiency, 1:449 galactosemia, 1:451–452 MCAD, 2:719 See also Genetic testing NF See Neurofibromatosis NF genes, 2:811–813 NFH gene, 1:81 Nibrin gene, 2:817 NIDDM See Non-insulin dependent diabetes mellitus Niemann-Pick disease (NPD), 2:813–816 Nifedipine, 2:1034 Night blindness, 2:1000 Night use brace, 2:1037 Niikawa, N., 1:625 Nijmegen breakage syndrome (NBS), 2:816–818 Nitrogen metabolism, 2:847–850 Noack syndrome, 1:205, 2:914 Nonclassical congenital adrenal hyperplasia-21, 1:262, 264 Noncommunicating hydrocephalus, 1:575–577 Nonimmune hydrops fetalis, 1:579–581, 2:809 Noninflammatory diffuse hair loss, 1:504–505 Noninflammatory patterned hair loss, 1:503–504 Non-insulin dependent diabetes mellitus (NIDDM) classification, 1:328 demographics, 1:333 diagnosis, 1:334–335 genetics, 1:331, 1:331–332, 1:335 insulin gene mutations, 1:332, 335, 345 signs and symptoms, 1:332–334 syndromes associated with, 1:332–333 Non-penetrance, FSH muscular dystrophy, 1:444–446 Nonsense mutations, 1:458–459 Nonsurgical hair additions, 1:508 Nonsyndromic hearing loss, 1:536–537 Nonverbal learning disability Asperger syndrome, 1:110 defined, 1:109 Noonan, C D., 2:1044 Noonan, Jacqueline, 2:818 Noonan syndrome, 2:818–821 vs Aarskog syndrome, 1:2 vs cardiofaciocutaneous syndrome, 1:199 defined, 1:200 Normal pressure hydrocephalus, 1:575–577 GALE ENCYCLOPEDIA OF GENETIC DISORDERS IO Obesity-hypotonia syndrome, 1:252–255 Obligate carrier, 1:306 Obsessive-compulsive disorder (OCD) vs Asperger syndrome, 1:110 Fahr disease, 1:406 Tourette syndrome, 2:1138 Obstruction heart defects, 1:266–267, 268 Occipital encephalocele, 1:387–388 Occipital horn syndrome, 2:729 Occupational hazards, cancer demographics, 1:191 Occupational therapy, muscular dystrophy, 2:775 OCD See Obsessive-compulsive disorder Ochronosis, alkaptonuria, 1:56–60 OCRL1 gene, 1:687–690 Ocular albinism, 1:44 Ocular hypertelorism, 1:2 Oculo-auriculo-vertebral spectrum, 1:491–493, 2: 1141 Oculo-digito-esophago-duodenal syndrome (ODED), 2:825–826 Oculocutaneous albinism, 1:44 Oculomandibulodyscephaly with hypotrichosis, 1:509–511 Oculomandibulofacial syndrome, 1:509–511 Oculopharyngeal muscular dystrophy classification, 2:770 genetic profile, 2:772 signs and symptoms, 2:773–774 ODED (Oculo-digito-esophagoduodenal syndrome), 2:825–826 Odontohypophosphatasia, 1:589 Okihiro syndrome, 1:355–356 Oligohydramnios sequence, 2:827–830 , 829 Ollier disease, 1:227–228 Omphalocele, 2:830–833 Beckwith-Wiedemann syndrome, 1:146–148 Carpenter syndrome, 1:207 Omphalopagus, conjoined twins, 1:273 Oncogenes, 1:478–479, 2:833–836 OPD (Otopalatodigital syndrome), 2:863–865 , 865 Opitz, John M., 2:1065, 1225 Opitz syndrome, 2:837–840 , 840 Oppenheim, Hermann, 1:370 Oppositional defiant disorder, 1:110 Opsin, rhodopsin, 2:1000 Optic atrophy, 1:652–655 Optic disc coloboma, 1:255 Oral alkalinization, 1:307 Oral-facial-digital syndrome, 2:841–843 , 843 Oral loading test, cystinuria, 1:306 Organ transplantation cystinosis, 1:304 major histocompatibility complex, 2:697, 699 Organic acidemias, 2:843–846 Ornithine transcarbamylase deficiency (OTC), 2:847–850, 2: 1159–1160 Osler-Weber-Rendu syndrome (OWR), 2:850–854 , 853 Ossification, achondrogenesis, 1:15 Osteoarthritis, 2:853–856 alkaptonuria diagnosis, 1:59 Ehlers-Danlos syndrome, 1:378 Marshall syndrome, 2:712–713 Osteogenesis imperfecta, 1:284–285, 2:856–859 , 859 Osteoma, 1:194 Osteoporosis, 2:860–863 , 862 ankylosing spondylitis, 1:94 homocystinuria, 1:563 Klinefelter syndrome, 1:638 metaphyseal dysplasia, 2:733 Werner syndrome, 2:1193–1194 Wilson disease, 2:1200 OTC (Ornithine transcarbamylase deficiency), 2:847–850, 2: 1159–1160 Otopalatodigital syndrome (OPD), 2:863–865 , 865 Otosclerosis, 1:537–538 Otospondylomegaepiphyseal dysplasia, 2:1190–1192 Ovarian cancer, 2:866–869 GALE ENCYCLOPEDIA OF GENETIC DISORDERS BRCA and genes, 1:174 genetic counseling, 1:470 hereditary component, 1:189 susceptibility testing, 1:478–479 Ovaries, polycystic, 2:935–938 , 937 Ovarioleukodystrophy, 1:662, 664 OWR (Osler-Weber-Rendu syndrome), 2:850–854 , 854 Oxidoreductases, 2:972–975 IP p16 gene, 1:192 p53 gene, 1:666–667 5p minus syndrome, 1:236, 1:289–291 Paget’s disease, 1:390 PAHX/PHYH gene, 2:982 Paine syndrome, 2:871–872 Palliative therapy, cancer management, 1:196, 880 Pallister, Philip D., 2:873 Pallister-Hall syndrome, 1:497–498, 2:873–874 Pancreatic beta cell agenesis, 2:875–877 Pancreatic cancer, 2:877–880 , 879–880 hereditary pancreatitis, 1:545 multiple endocrine neoplasia-1, 2:763 Pancreatic disease cancer (See Pancreatic cancer) hereditary pancreatitis (See Hereditary pancreatitis) insulin-dependent diabetes mellitus, 1:331 non-insulin dependent diabetes mellitus, 1:332–333 Von Hippel-Lindau syndrome, 2:1175–1177 Panic attacks, 2:881–884 Panic disorder, 2:881–884 Papillon-Lefevre syndrome, 1:501–503 Paranoid schizophrenia, 2:1023 Parapagus, conjoined twins, 1:273 Parasitic twins, 1:273 Parathyroid glands, Fahr disease, 1:407 Parathyroid hormone, multiple endocrine neoplasia-1, 2:766 Parentage, human leukocyte antigen, 2:699 Parkinson disease (PD), 2:884–887 vs Alzheimer disease, 1:65 vs Azorean disease, 1:136 color blindness, 1:258 Paroxysmal nocturnal hemoglobinuria (PNH), 2:888–890 Partial androgen insensitivity, 1:83–86 1335 Index Norman-Landing disease, 1:487–490, 2:807 Norrie disease (ND), 2:822–824 Nosebleeds, 2:852–853 NPD (Niemann-Pick disease), 2:813–816 NPR1 gene, 2:986 Nucleic acids, 1:342–343 Nucleotide sequence Azorean disease, 1:135 bipolar disorder type II, 1:160 fragile X syndrome, 1:431 Nurogenic arthrogryposis, 1:106 Nutrition See Diet and nutrition Nyhan, William, 1:660 Nystagmus albinism, 1:44 Cornelia de Lange syndrome, 1:280 Index Partial 11q monosomy syndrome, 1:615–618 Partial trisomy 18, 2:1146 Patau, Klaus, 2:890 Patau syndrome, 1:234, 2:890–893 , 892 Patent ductus arteriosus (PDA), 2:893–896 , 895 achondrogenesis, 1:15 characteristics, 1:266 Cornelia de Lange syndrome, 1:280 signs and symptoms, 1:268 PAX3 gene, 2:1184 PCCA gene, 2:955–957 PCCB gene, 2:955–957 PCD (Pyruvate carboxylase deficiency), 2:970–972 PCOS (Polycystic ovary syndrome), 2:935–938 , 937 PCR/FRET analysis, 2:719 PD See Parkinson disease PDA See Patent ductus arteriosus PDD See Pervasive developmental disorders PDHA1 gene, 2:973–974 Pearson’s syndrome, 1:87 Pectus carinatum Marfan syndrome, 2:708, 711 Schwartz-Jampel syndrome, 2:1029–1031 Pectus excavatum, Marfan syndrome, 2:708, 711 Pediatric genetic counseling, 1:470 Pedigree analysis, 2:896–899 , 898 genetic counseling, 1:470–471 inheritance patterns, 1:610–611 multifactorial inheritance, 2:760 Pegvisomant, acromegaly, 1:32 Pelizaeus, F., 2:899 Pelizaeus-Merzbacher disease (PMD), 1:547–549, 2:899–901 Pendred syndrome, 2:902–906 D-Penicillamine cystinuria, 1:307 scleroderma, 2:1033–1034 Wilson disease, 2:1200–1201 Penicillin, sickle cell disease, 2:1054 Pepper syndrome, 1:252–255 Perinatal hypophosphatasia, 1:588 Periodontosis, Haim-Munk syndrome, 1:501–503 Peripheral myelin protein 22, CharcotMarie-Tooth disease, 1:219 Peripheral nervous system, CharcotMarie-Tooth disease, 1:219 Peripheral stem cell transplantation, 1:197–198 Perlecan protein, 2:1029 1336 Perlman syndrome, 1:148 Peroxisome targeting sequence 2, rhizomelic chondrodysplasia punctata, 2:997–999 Peroxisomes adrenoleukodystrophy, 1:37 infantile refsum disease, 1:603–605 rhizomelic chondrodysplasia punctata, 2:997–999 Zellweger syndrome, 2:1225–1227 Pervasive developmental disorders (PDD), 2:906–910 Asperger syndrome, 1:109 autism, 1:130 not otherwise specified, 2:907–908 Peutz-Jeghers syndrome (PJS), 2:910–913 defined, 1:194 stomach cancer, 2:1099 PEX1 and genes infantile refsum disease, 1:604–605 Zellweger syndrome, 2:1226 PEX7 gene, 2:997–999 Pfeiffer syndrome, 2:914–917 classification, 1:205 craniosynostosis, 1:287 fibroblast growth factor receptor mutations, 1:429–430 Jackson-Weiss syndrome, 1:613–615 Pharmacogenetics, 2:917–918 Phenocopy, 1:252, 1:278–282 Phenothiazines, 2:944 Phenotype, 1:482–483 Phenotypic variance, 1:483 Phenylalanine alkaptonuria, 1:57 phenylketonuria, 2:922 Phenylalanine hydroxylase, phenylketonuria, 2:919–923 Phenylketonuria (PKU), 2:919–923 autism, 1:131 galactokinase deficiency, 1:449 Pheochromocytoma multiple endocrine neoplasia-2A, 2:764–766 Von Hippel-Lindau syndrome, 2:1175–1177 PHEX gene, 1:591–593 Phocomelia See Roberts SC phocomelia Phosphate deficiency, McCuneAlbright syndrome, 2:721–722 Photorefractive keratectomy, 2:783–784 Photosensitivity, 1:21–23 Physical therapy muscular dystrophy, 2:775 Parkinson disease, 2:886 Phytanic acid, Refsum disease, 2:982–985 PI gene, 1:61–62 PI M gene, 1:61 Pi M protein, 1:61 Pi protein, 1:61 PI S gene, 1:61–62 PI Z gene, 1:61–62 Pick’s disease, 1:316, 318 Piebaldism, 1:45 Pierre-Robin sequence, 2:922–925 Stickler syndrome, 2:1095 Weissenbacher-Zweymuller syndrome, 2:1191–1192 PIG-A gene, 2:888–889 Pigmentation, 1:419, 2:807–811, 814–815, 1185 Pili torti, Menkes syndrome, 2:730 Pituitary dwarfism, 2:926–929 , 927–928 Pituitary gland acromegaly and, 1:29–32 multiple endocrine neoplasia-1, 2:763–764, 766–767 pituitary dwarfism, 2:926–929, 2:927–928 PJS See Peutz-Jeghers syndrome PKD1 gene, 2:932 PKD (Polycystic kidney disease), 2:931–934 , 933–934 PKD (Pyruvate kinase deficiency), 2:975–977, 2: 1143 PKLR gene, 2:976 PKM2 gene, 2:976 Plaque formation, Alzheimer disease, 1:65 Plasma exchange, myasthenia gravis, 2:779 Plasmapheresis, 2:985 Platelets albinism, 1:44 thrombasthenia of Glanzmann and Naegli, 2:1133–1136 Pleurisy, familial Mediterranean fever, 1:416 PLOD gene, 1:378 PLP gene, 2:899–901 PLP null syndrome, 2:900 PMD (Pelizaeus-Merzbacher disease), 1:547–549, 1:899–901 PNH (Paroxysmal nocturnal hemoglobinuria), 2:888–890 Poikiloderma, 2:1010 Point mutation, 1:458–459 Poland, Alfred, 2:929 Poland anomaly, 2:929–931 Poland-Möebius syndrome, 2:748 Polycystic fibrous dysplasia, 1:30 Polycystic kidney disease (PKD), 2:931–934 , 933–934 GALE ENCYCLOPEDIA OF GENETIC DISORDERS Predictive testing myotonic dystrophy, 2:787 spinocerebellar ataxia, 2:1086 Prednisone, muscular dystrophy, 2:774–775 Pregnancy associated plasma protein-A, 1:280 molar, 2:1229 phenylketonuria and, 2:922 See also Maternal age; terms beginning with Prenatal Preimplantation genetic diagnosis sickle cell disease, 2:1052 zygote formation, 1229 See also Genetic testing Premature centromeric separation, 1:72 Premature rupture of membranes, 2:827–830 Prematurity, cerebral palsy, 1:214–215 Premutation, fragile X syndrome, 1:431–432 Prenatal genetic counseling, 1:469, 471 See also Genetic counseling Prenatal growth retardation, 1:106 Prenatal testing chromosome analysis, 1:237–238, 479–480 congenital adrenal hyperplasia, 1:264–265 Cornelia de Lange syndrome, 1:280 deletion 22q11 syndrome, 1:314 fibroblast growth factor receptor mutations, 1:428–430 galactosialodosis, 2:810 genetic testing, 1:474 hypochondroplasia, 1:586–587 Miller-Dieker syndrome, 2:746 myotonic dystrophy, 2:787 neuraminidase deficiency, 2:806 Opitz syndrome, 2:840 osteogenesis imperfecta, 2:858–859 Pelizaeus-Merzbacher disease, 2:901 Pfeiffer syndrome, 2:916–917 Rieger syndrome, 2:1002 severe combined immunodeficiency, 2:1043 Sjögren-Larsson syndrome, 2:1063 Smith-Lemli-Opitz syndrome, 2:1067 spina bifida, 2:1080–1081 spinocerebellar ataxia, 2:1087 spondyloepiphyseal dysplasia, 2:1090–1091 Stickler syndrome, 2:1096–1097 Williams syndrome, 2:1197 Wiskott-Aldrich syndrome, 2:1203–1204 See also Genetic testing Presenilin gene, 1:66 Presenilin gene, 1:66 Presymptomatic genetic testing, 1:478 GALE ENCYCLOPEDIA OF GENETIC DISORDERS Preventive surgery, cancer management, 1:196 Priapism, sickle cell disease, 2:1051 Primary ciliary dyskinesia, 1:630–632 Primary dementia, 1:316 Primary immunodeficiency diseases, 2:1040 Primary liver cancer, 1:677 Prion diseases, 2:949–952 Prion protein, 2:949–952 PRNP gene, 2:950–952 Proband, Alagille syndrome, 1:42 Problem drinkers, 1:48 Progeria syndrome, 2:952–954 , 954, 2:1193 Programmed cell death, 2:834 Progressive diaphyseal dysplasia, 1:389–391 Propionic acidemia, 2:844–845, 2:955–957 Propionyl CoA carboxylase deficiency, 2:955–957 Prostate cancer, 2:957–960 BRCA and genes, 1:174 hereditary component, 1:189 Prostate-specific antigen (PSA), 2:959 Prostatectomy, 1:195 Protective protein/cathepsin A galactosialodosis, 2:807–811 neuraminidase deficiency, 2:803–804 Proteus syndrome, 2:961–963 Proto-oncogenes cancer genetics, 1:190 oncogene formation, 2:833–836 Protonapia (blue color blindness), 1:257 Protoporphyrinogen oxidase, 2:942 Protrusio acetabluae, Marfan syndrome, 2:708, 711 Prune-belly syndrome, 2:963–965 , 965 Prusiner, Stanley, 2:949 PSA (Prostate-specific antigen), 2:959 PSE (Pseudoxanthoma elasticum), 2:965–968 Pseudo-Hurler disease, 1:487–490, 2:807 Pseudodominance, 1:611 Pseudohemophilia, 2:1177 Pseudohypertrophy, 1:361 Pseudohypophosphatasia, 1:589 Pseudothalidomide syndrome, 1:70 Pseudoxanthoma elasticum (PSE), 2:965–968 Psoriasis accutane embryopathy, 1:13 ankylosing spondylitis, 1:94, 96 hair loss, 1:505 1337 Index Polycystic ovary syndrome (PCOS), 2:935–938 , 937 Polydactyly acrocallosal syndrome, 1:27 Ellis-van Creveld syndrome, 1:382, 382 gene mutation, 1:459, 459 Meckel-Gruber syndrome, 2:727–728 Polygenic trait alcoholism, 1:49 asthma, 1:116 Polyhydramnios achondrogenesis, 1:15 thanatophoric dysplasia, 2:1131 Polymer, alkaptonuria, 1:57 Polymyositis, Raynaud disease, 2:979 Polyostotic fibrous dysplasia, 1:30, 2:720–722 , 722 Polyploidy, chromosomal abnormalities, 1:235, 1:235–236 Polyps, Peutz-Jeghers syndrome, 2:910–913 Polysyndactyly, 1:496–498 Pompe, J C., 1:23 Pompe disease, 1:23–26 Popliteal pterygium syndrome, 2:1167 Population genetics, 1:460 Porphyria cutanea tarda, 2:941–942, 944 Porphyrias, 2:938–944 causes and symptoms, 2:941–942 characteristics, 2:938–939 classification, 2:939–941 Port-wine stains, Sturge-Weber syndrome, 2:1103–1105 Post-axial polydactyly type A Greig cephalopolysyndactyly syndrome, 1:497 Pallister-Hall syndrome, 2:873–874 Posterior embryotoxon, Alagille syndrome, 1:42 Posterior polymorphous dystrophy, 1:275–277 Postmenopausal osteoporosis, 2:860–863 Postnatal conditions, cerebral palsy, 1:214 Potassium, long-QT syndrome, 1:686 PPGB gene, 2:808–809 Prader-Willi syndrome, 2:945–948 chromosomal deletions, 1:236–237 vs Cohen syndrome, 1:255 genetic imprinting, 1:91 Pre-mRNA, 1:456 Prechordal plate, holoprosencephaly, 1:557 Precocious puberty, 2:1016 Index Psychological problems accutane use, 1:10 alcoholism, 1:48 Alzheimer disease, 1:69 Asperger syndrome, 1:109 bipolar disorder, 1:160 celiac disease, 1:209 deletion 22q11 syndrome, 1:313 dementia, 1:65, 316 Fahr disease, 1:406 homocystinuria, 1:563 Lesch-Nyhan syndrome, 1:661–662 panic disorder, 2:881–884 Prader-Willi syndrome, 2:947–948 schizophrenia, 2:1023–1027 Schwartz-Jampel syndrome, 2:1030 Smith-Fineman-Myers syndrome, 2:1064–1065 Smith-Magenis syndrome, 2:1070–1071 Tourette syndrome, 2:1136–1139 Wilson disease, 2:1200 XYY syndrome, 2:1222–1223 Psychosocial treatment alcoholism management, 1:53–54 bipolar disorder type II, 1:162 hair loss therapy, 1:508 pervasive developmental disorders, 2:909 Proteus syndrome, 2:963 sickle cell disease, 2:1055 See also Psychotherapy Psychostimulants, Asperger syndrome, 1:111 Psychotherapy Asperger syndrome, 1:111 schizophrenia, 2:1027 Tourette syndrome, 2:1139 PTEN gene, 1:174 Ptosis, Cornelia de Lange syndrome, 1:280 Puberty, precocious, 2:1016 Pudlak, P., 1:550 Pulmonary artery banding, congenital heart defects, 1:269 Pulmonary atresia, 1:112 Pulmonary valve stenosis Cornelia de Lange syndrome, 1:280 Noonan syndrome, 2:819 PWS See Prader-Willi syndrome Pygopagus, conjoined twins, 1:273 Pyle, Edwin, 2:733 Pyle’s disease, 2:733–735 Pyloric stenosis, 2:968–970 , 969 Cornelia de Lange syndrome, 1:279 multifactorial inheritance, 2:761 Smith-Lemli-Opitz syndrome, 2:1068 Pyridostigmine, myasthenia gravis, 2:778 1338 Pyridoxine therapy homocystinuria, 1:564 sideroblastic X-linked anemia, 1:88 Pyrin protein, familial Mediterranean fever, 1:415 Pyruvate carboxylase deficiency (PCD), 2:970–972 Pyruvate dehydrogenase complex deficiency, 2:970, 2:972–975 Pyruvate kinase deficiency (PKD), 2:975–977, 2: 1143 IQ 11q deletion syndrome, 1:615–618 12q24 locus, cardiofaciocutaneous syndrome, 1:199 QRS complex, long-QT syndrome, 1:685–686 Quinacrine, alkaptonuria -related ochronosis, 1:59 IR Rab Escort protein-1 (REP-1), choroideremia, 1:231 Rabson-Mendenhall syndrome insulin gene mutations, 1:345 non-insulin dependent diabetes mellitus, 1:332–333 Radial keratotomy, 2:783 Radiation therapy acromegaly, 1:31 cancer management, 1:195–196 liver cancer, 1:680 ovarian cancer, 2:868 pancreatic cancer, 2:880 prostate cancer, 2:960 stomach cancer, 2:1102 Raloxifen, osteoporosis, 2:862–863 Rapid eye movement sleep, 2:791–793 Rapp-Hodgkin syndrome, 1:373–374 RAS oncogenes, 2:834 Rathbun, J C., 1:587 Raynaud disease, 2:979–982 , 980–981, 2:1032, 1034 Recessively inherited multiple epiphyseal dysplasia, 1:337 Recombinant DNA technology, Donohue syndrome, 1:347 Recombinant human insulin-like growth factor 1, Donohue syndrome, 1:347 Recombination, 1:459 RecQL4 gene, 2:1010 Recurrence risk, multifactorial inheritance, 2:761 Refractive eye surgery, 2:783–784 Refsum, Sigvald, 2:982 Refsum disease, 2:982–985 infantile refsum disease, 1:603–606 vs Niemann-Pick disease, 2:816 Reis-Buckler’s dystrophy, 1:275–277 REM sleep, 2:791–793 Renal cell carcinoma, 2:1175–1177 Renal failure Bardet-Biedl syndrome, 1:139 cystinuria, 1:305 familial Mediterranean fever, 1:416 hemolytic-uremic syndrome, 1:521–523 hereditary spherocytosis, 2:1077 hypertension, 2:985–987 muscle CPT deficiency, 1:203 polycystic kidney disease, 2:933–934 prune-belly syndrome, 2:964–965 Renpenning, Hans, 2:987 Renpenning syndrome, 2:987–989, 2:1106 Reproductive function cancer demographics, 1:191 cystic fibrosis, 1:298 Kartagener syndrome, 1:630–632 Klinefelter syndrome, 1:637–638 polycystic ovary syndrome, 2:935–938 Research Units in Pediatric Psychopharmacology, 2:909 Residual schizophrenia, 2:1024 Respiratory care, muscular dystrophy, 2:775 Respiratory insufficiency, thanatophoric dysplasia, 2:1131 Respiratory tract cystic fibrosis, 1:296–300 Patau syndrome, 2:892 scleroderma, 2:1033–1034 Responsive dementia, 1:320 Restriction enzymes, Human Genome Project, 1:566 Restriction fragment length polymorphisms genetic mapping, 1:457 Human Genome Project, 1:566 RET gene cancer susceptibility testing, 1:478 Hirschsprung’s disease, 1:554–556 multiple endocrine neoplasia-2, 2:765–766 oncogenesis, 2:836 Retina, albinism, 1:44 Retinal angiomas, 2:1172–1173 Retinal coloboma, 1:255 Retinal detachment, 2:710 GALE ENCYCLOPEDIA OF GENETIC DISORDERS RNA (Ribonucleic acid), 2:1004, 1004–1005 DNA structure and, 1:344 gene structure and, 1:455 Roberts SC phocomelia, 1:70, 72, 2:1005–1007 Robinow, Meinhard, 2:1007 Robinow syndrome, 2:1007–1009 , 1008 Rod cells, rhodopsin, 2:999–1000 Ross procedure, congenital heart defects, 1:269 Rothmund-Thomson syndrome (RTS), 2:1009–1011 RSK2 gene, 1:249 RSS (Russell-Silver syndrome), 2:1014–1016 RSTS (Rubinstein-Taybi syndrome), 2:1012–1014 , 1015 RTS (Rothmund-Thomson syndrome), 2:1009–1011 Rubinstein, Jack, 2:1012 Rubinstein-Taybi syndrome (RSTS), 2:1012–1014 , 1015 Russell, A., 2:1014 Russell-Silver syndrome (RSS), 2:1014–1016 Ryanodine receptor protein, malignant hyperthermia, 2:701–702 IS 12S gene, 1:568 Sacroiliac joint, 1:94 Sacroiliitis, 1:94, 96 Saethre, Haakon, 2:1019 Saethre-Chotzen syndrome, 2:1019–1021 arthrogryposis multiplex congenita, 1:105–106 Rubinstein-Taybi syndrome, 2:1013–1014 Sagittal craniosynostosis, 1:287–288 St John’s wort, depression management, 1:327 Saldino, R M., 2:1044 Salonen-Herva-Norio syndrome, 1:578–579 Sanfilippo syndrome, 2:755–756 Sanger Centre, 1:565–566 Sarcoidosis, 2:794 Sarcoma angiosarcoma, 1:39, 41 chondrosarcoma, 1:227–229, 1: 542 classification, 1:189 Li-Fraumeni syndrome, 1:665–666 Savant skills, autism, 1:130 GALE ENCYCLOPEDIA OF GENETIC DISORDERS SBG (Simpson-Golabi-Behmel syndrome), 2:1056–1059 SBMA (Spinobulbar muscular atrophy), 1:634–636, 2:1081 SCA (Spinocerebellar ataxia), 2:1084–1087 Scaphocephaly Russell-Silver syndrome, 2:1015 sagittal craniosynostosis, 1:287 Scapuloiliopereoneal atrophy with cardiopathy See Emery-Dreifuss muscular dystrophy Schaefer, G Bradley, 1:536 Scheie syndrome, 2:754 Schilder’s disease, 1:185 Schinzel acrocallosal syndrome, 1:26–28 , 28 Schinzel-Giedion syndrome, 2:1022 Schizophrenia, 1:48, 2:908, 2:1023–1027 Schmid type dysplasia, 2:733–734 Schwachman Diamond metaphyseal dysplasia, 2:733–734 Schwalbe ring, posterior embryotoxon, 1:42–43 Schwartz-Jampel syndrome (SJS), 2:1028–1031 Schwatz, V., 1:447 SCID (Severe combined immunodeficiency), 2:1040–1043 Scleroderma, 2:1031–1034 , 1032 hair loss, 1:502 progeria syndrome, 2:953 Raynaud disease, 2:979 SCN5A gene Brugada syndrome, 1:267–268 long-QT syndrome, 1:683 Scoliometer, 2:1036 Scoliosis, 2:1034–1037 , 1035 arthrogryposis multiplex congenita, 1:105 Beals syndrome, 1:142–143 central core disease, 1:212 cerebral palsy, 1:215–216 cleidocranial dysplasia, 1:244 deletion 22q11 syndrome, 1:314 diastrophic dysplasia, 1:337 Duchenne muscular dystrophy, 1:361 Ehlers-Danlos syndrome, 1:378 Emery-Dreifuss muscular dystrophy, 1:386 Engelmann disease, 1:389 Friedreich ataxia, 1:439 Fryns syndrome, 1:443 Goldenhar syndrome, 1:493 Holt-Oram syndrome, 1:560–561 homocystinuria, 1:563 Klippel-Feil sequence, 1:640 1339 Index Retinal dysplasia, 2:892 Retinal molecule, rhodopsin, 2:1000 Retinal photograph, glaucoma, 1:487 Retinal pigmented epithelium, choroideremia, 1:229–231 Retinitis pigmentosa, 2:989–991 abetalipoproteinemia, 1:6 Bardet-Biedl syndrome, 1:138 choroideremia, 1:230 color blindness, 1:258 cone-rod dystrophy, 1:260–261 infantile refsum disease, 1:605 Leber congenital amaurosis, 1:649–652 Refsum disease, 2:984 rhodopsin mutations, 2:1000 Sjögren-Larsson syndrome, 2:1062 Usher syndrome, 2:1160–1165 Retinoblastoma, 2:991–994 , 992–994 Retinopathy, sickle cell disease, 2:1052 Retraction syndrome, Duane, 1:353–357 , 356 Retroviruses, gene therapy, 1:464 Rett, Andreas, 2:995 Rett syndrome, 2:995–996 autism, 1:131 characteristics, 2:907–910 Reversible dementia, 1:320 Reynolds, J F., 1:199 Rh protein, hydrops fetalis, 1:579–581 Rhabdomyolysis, 1:203 Rheumatoid arthritis ankylosing spondylitis, 1:94 Raynaud disease, 2:979 Rheumatoid factor, ankylosing spondylitis, 1:94 Rhizomelic chondrodysplasia punctata, 2:997–999 Rhizomelic shortening, 1:18, 20–21 Rho/Rac guanine exchange factor, Aarskog syndrome, 1:1–2 Rhodopsin, 2:999–1000 Ribonucleic acid (RNA) See RNA (Ribonucleic acid) Ribosomal RNA (rRNA), 1:456, 2:1004–1005 Rich, Alexander, 1:344 Rickets, 1:587 RIEG1 and genes, 2:1001–1003 Rieger, Herwigh, 2:1001 Rieger syndrome, 2:1001–1003 Riley-Day syndrome, 1:412–413 Rilutek, amyotrophic lateral sclerosis, 1:82 Risedronate, osteoporosis, 2:862–863 Ristocetin-induced platelet aggregation, 2:1180–1181 Index Scoliosis (cont’d) Marfan syndrome, 2:708, 711 metaphyseal dysplasia, 2:733 Noonan syndrome, 2:820–821 Schwartz-Jampel syndrome, 2:1028–1031 Sebastian syndrome, 2:1037–1038 Seckel, Helmut G P., 2:1039 Seckel syndrome, 2:1030, 2:1039–1040 Second-degree relative, Alagille syndrome, 1:42 Secondary dystonia, 1:370 SED See Spondyloepiphyseal dysplasia Seemanova syndrome, 2:871–872 Seizures Aicardi syndrome, 1:40 Angelman syndrome, 1:92 epileptic, 1:394–396 lissencephaly, 1:675–676 long-QT syndrome, 1:684–686 neurofibromatosis, 2:812 Smith-Fineman-Myers syndrome, 2:1064–1065 Sturge-Weber syndrome, 2:1104–1105 tuberous sclerosis complex, 2:1152–1153 Selective serotonin reuptake inhibitors (SSRIs) Asperger syndrome, 1:111 depression management, 1:327 hair loss treatment, 1:508 Self-injurious behavior, Tourette syndrome, 2:1138 Senile osteoporosis, 2:860–863 Sensorineural hearing loss Pendred syndrome, 2:902–906 Usher syndrome, 2:1160–1165 Septal defects, 1:267, 268 Serotonin dopamine antagonists, schizophrenia, 2:1027 Serum amyloid A, familial Mediterranean fever, 1:416 Serum CK test, acid maltase deficiency, 1:25–26 Serum glutamine oxaloacetic transaminase alcoholism diagnosis, 1:52 alpha-1 antitrypsin, 1:63 Serum glutamine pyruvic transaminase, 1:63 Severe achondroplasia with developmental delay and acanthosis nigricans dysplasia, 1:429 Severe asthma, 1:120 Severe combined immunodeficiency (SCID), 2:1040–1043 , 1042 Sex chromosomes aneuploidy, 1:234–325 1340 Crane-Heise syndrome, 1:286 genetic disorders, 1:472–473 genotype and phenotype, 1:482–483 Klinefelter syndrome, 1:637–638 structure and number, 1:239 Sex determination, 2:1228 Sex-linked inheritance carrier testing, 1:477–478 Duchenne muscular dystrophy, 1:360 Menkes syndrome, 2:729–730 X-linked dominant, 1:607–609 X-linked recessive, 1:609 X-linked semi-dominant, 1:609–610 Sexual behavior, cancer demographics, 1:191 Sexual development, sex determining region Y, 2:1092–1093 SFMS (Smith-Fineman-Myers syndrome), 2:1064–1065 Shaw, S., 2:1112 Shh pathway, holoprosencephaly, 1:557 Short rib polydactyly syndromes (SRPS), 1:380, 382, 2:1044–1045, 1044–1046 SHOX gene, 1:658–660 Shprintzen-Goldberg craniosynostosis syndrome, 2:1046–1048 Shprintzen syndrome See Deletion 22q11 syndrome Shunt procedures, congenital heart defects, 1:269 Sialic acid, neuraminidase deficiency, 2:803 Sialidase, neuraminidase deficiency, 2:803 Sialodosis I and II vs galactosialodosis, 2:809 neuraminidase deficiency, 2:802–806 Sibling pair studies, 2:762 Sickle cell disease, 2:1048–1055 , 1049–1050 , 1054 amniocentesis, 1:75 color blindness, 1:258 nephrogenic diabetes insipidus, 2:794 Sickle cell trait, 2:1048 Sickledex test, sickle cell disease, 2:1052 Sideroblastic X-linked anemia, 1:86–89 Siewert syndrome, 1:630–632 Sigmoidoscopy familial adenomatous polyposis, 1:411 hereditary colorectal cancer, 1:533 Signal transducers, proto-oncogenes, 2:834 Silver, H K., 2:1014 Simpson-Golabi-Behmel (SGB) syndrome, 1:148, 2:1056–1059 , 1057 Single point mutation, 2:717 Sinuses, cystic fibrosis, 1:297 Sipple syndrome, 2:763–767 Sirenomelia, 2:1059, 1059–1061 Siris, Evelyn, 1:251 Sister chromatid exchange, Bloom syndrome, 1:163, 165 Situational drinkers, 1:48 Situs inversus, Kartagener syndrome, 1:630–632 Sjögren, Torsten, 2:1061 Sjögren-Larsson syndrome, 2:1061–1063 SJS (Schwartz-Jampel syndrome), 2:1028–1031 Skeletal dysplasia, 1:366–368, 1:367 Ellis-van Creveld syndrome, 1:382–383 hypochondroplasia, 1:584–587 Larsen syndrome, 1:646–649 Schwartz-Jampel syndrome, 2:1028–1031 Skin cancer Fanconi anemia, 1:419 hereditary component, 1:189 Skin conditions blue rubber bleb nevus syndrome, 1:166–167 Donohue syndrome, 1:346–347 Dubowitz syndrome, 1:359 ectodermal dysplasia, 1:374–375 familial Mediterranean fever, 1:416 Haim-Munk syndrome, 1:501–503 Harlequin fetus, 1:513–515, 514 ichthyosis, 1:597–599 McCune-Albright syndrome, 2:721 microphthalmia with linear skin defects, 2:741–743 Muir-Torre syndrome, 2:758–760 multiple lentigenes syndrome, 2:768–769 neurofibromatosis, 2:811–813, 812 Peutz-Jeghers syndrome, 2:910–913 progeria syndrome, 2:953 Proteus syndrome, 2:961–963 pseudoxanthoma elasticum, 2:965–967 Rothmund-Thomson syndrome, 2:1009–1011 scleroderma, 2:1032–1034 Sjögren-Larsson syndrome, 2:1061–1063 tuberous sclerosis complex, 2:1150–1151 Turner syndrome, 2:1156 GALE ENCYCLOPEDIA OF GENETIC DISORDERS Spahr type metaphyseal chondrodysplasia, 2:735 Spastic cerebral palsy, 2:1074–1075 Spastic gait genes, 1:547–549 Spectrin, hereditary spherocytosis, 2:1076 Sperm injections, 1:632, 2:1229 Spherocytosis, hereditary, 2:1075–1078 Sphygmomanometers, 1:398 Spielmeyer-Vogt-Sjögren-Batten disease, 1:139–141 , 141 Spina bifida, 1:387, 2:1078–1081 , 1080 anencephaly and, 1:90 Arnold-Chiari malformation, 1:103 characteristics, 2:800–801, 2:801 diastrophic dysplasia, 1:337 management, 2:802 multifactorial inheritance, 2:761–762 Waardenburg syndrome, 2:1185–1186 Spina bifida occulta, 2:1079 Adams-Oliver syndrome, 1:34 Alagille syndrome, 1:42–43 Spina rachischisis, 2:1078–1079 Spinal fusion, scoliosis, 2:1037 Spinal muscular atrophy (SMA), 2:1037, 2:1081–1084 Spinobulbar muscular atrophy (SBMA), 1:634–636, 2:1081 Spinocerebellar ataxia (SCA), 2:1084–1087 See also Azorean disease Spleen asplenia, 1:113 sickle cell disease, 2:1050 Tangier disease, 2:1111 Splenic sequestration, sickle cell disease, 2:1050 Splenomegaly, beta thalassemia, 1:151–152 Spondyloarthritis, 1:94 Spondyloepiphyseal dysplasia, 2:1088–1091, 2: 1094 Spondyloepiphyseal dysplasia tarda, 2:1088–1091 Spondylolisthesis, 2:708, 711 Spondylospinal thoracic dysostosis, 1:106 Spongy degeneration of the brain, 1:185–188 Sporadic inheritance central core disease, 1:211–212 Emery-Dreifuss muscular dystrophy, 1:384 pseudoxanthoma elasticum, 2:966 SRPS See Short rib polydactyly syndromes GALE ENCYCLOPEDIA OF GENETIC DISORDERS SRY (Sex determining region Y), 2:1091–1093 , 1093, 2:1218–1221 STA gene, 1:384 STA-MCA anastomosis, 2:750 Stallings, Patricia, 2:737 Statins, hyperlipoproteinemia, 1:584 Stein, I F., 2:935 Stein-Leventhal syndrome, 2:935–938 , 937 Steinert’s disease See Myotonic dystrophy Stem cell transplantation, 1:197–198 Stenosis congenital heart disease, 1:266–267 pyloric (See Pyloric stenosis) S.T.E.P.S program, 2:1129 Stickler syndrome, 2:1094–1097, 2:1191 Still, George, 1:127 Stillbirth, 1:13 Stilling-Turk-Duane syndrome, 1:353–357 , 356 STK11 gene, 2:911 Stomach cancer, 1:193, 2:1097–1103 , 1098–1099 , 1101 Strabismus albinism, 1:44–47 Duane retraction syndrome, 1:353–354 retinoblastoma, 2:992–993 Williams syndrome, 2:1197–1198 Streissguth, Ann, 1:424 Striae, Marfan syndrome, 2:710 Strickler syndrome, 2:713 Stroke, 2:1051 Stromal dystrophies, 1:276 STS content mapping, Human Genome Project, 1:566 Sturge-Weber syndrome (SWS), 1:256, 2:1103–1105 , 1104 Sturtevant, A H., 1:342 Stuve-Wiedemann syndrome, 2:1030 Subaortic stenosis, 1:266–267 Substance Abuse Subtle Screening Inventory, 1:52 Substantia nigra, 2:884–885 Sudden infant death syndrome Jervell and Lange-Nielsen syndrome, 1:619 long-QT syndrome, 1:683–684 Suicide, bipolar disorder type II, 1:161 L-Sulfoiduronate, Hunter syndrome, 1:567–568 Summitt syndrome, 1:205 Super-male syndrome, 2:1221–1223 Superconducting Quantum Interference Device, 1:152 1341 Index Waardenburg syndrome, 2:1183–1187 Werner syndrome, 2:1194 xeroderma pigmentosum, 2:1212–1213 Skin fibroblast testing, cystinosis, 1:303 SLC3A1 gene, 1:305 SLC6A4 gene, 2:881–884 SLC7A9 gene, 1:305 Sleep apnea achondroplasia, 1:19–20 Apert syndrome, 1:97 hypochondroplasia, 1:586–587 Marfan syndrome, 2:710 Slone Survey, accutane embryopathy demographics, 1:11 SLOS (Smith-Lemli-Opitz syndrome), 2:1065–1068 Sly disease beta-glucuronidase, 2:756 hydrops fetalis, 1:580–581 SMA (Spinal muscular atrophy), 2:1037, 2:1081–1084 Smith, Ann M., 2:1068 Smith, David W., 2:1065 Smith-Fineman-Myers syndrome (SFMS), 2:1064–1065 Smith-Lemli-Opitz syndrome (SLOS), 2:1065–1068 Smith-Magenis syndrome, 1:236, 2:1068–1071 Smoking alpha-1 antitrypsin, 1:62 asthma and, 1:121 cancer demographics, 1:190 cleft lip and palate, 1:241 hyperlipoproteinemia, 1:584 Marfan syndrome, 2:711 osteoporosis, 2:862 Sneezing, 1:21–23 Social drinkers, 1:49 SOD1 gene, 1:80–82 Sodium valproate, bipolar disorder type II, 1:161–162 Somatomedin C See Insulin-like growth factor-1 Somatostatin, acromegaly, 1:30 Soni, T., 1:448 Sotos syndrome, 2:1071–1074 , 1073 vs Beckwith-Wiedemann syndrome, 1:148 vs Cohen syndrome, 1:255 Marshall-Smith syndrome, 2:716 SOX9 gene campomelic dysplasia, 1:183 sexual development, 2:1093 SOX10 gene Hirschsprung’s disease, 1:553 Waardenburg syndrome, 2:1184 Index Superficial temporal artery-middle cerebral arteryanastomosis, 2:750 Support Organization for Trisomy 18, 13, and Related Disorders (S.O.F.T.), 2:1149 Supravalvar aortic stenosis, 2:1197 Surgery Aarskog syndrome, 1:2–3 cancer management, 1:196 congenital heart defects, 1:269 eye, 2:783–784 laser, 2:993 liver cancer, 1:680 long-QT syndrome, 1:686 Marfan syndrome, 2:711 Moyamoya, 2:750 muscular dystrophy, 2:775 ovarian cancer, 2:868 pancreatic cancer, 2:879 Parkinson disease, 2:887 prostate cancer, 2:960 sickle cell disease, 2:1055 stomach cancer, 2:1102 Survival of motor neuron protein, 2:1083 Sutherland Haan X-linked mental retardation syndrome, 2:988, 2:1105–1107 , 1106 Sweat glands, cystic fibrosis, 1:298 Syncope, long-QT syndrome, 1:684–685 Syndactyly acrocallosal syndrome, 1:27 Apert syndrome, 1:97 arthrogryposis multiplex congenita, 1:106 Fraser syndrome, 1:435–436 Nijmegen breakage syndrome, 2:817–818 oculo-digito-esophago-duodenal syndrome, 2:825–826 Syndromatic hepatic ductular hypoplasia, 1:41–43 Syndromic hearing loss, 1:536 Syringomyelia, 1:101 System for Thalidomide Education and Prescribing Safety program, 2:1129 Systemic elastorrhexis, 2:965–968 IT 1278T gene, 1:563, 565 Talipes calacaneus, 1:245 Talipes equinovarus arthrogryposis multiplex congenita, 1:105 clubfoot, 1:245 Tamoxifen, breast cancer management, 1:177 1342 Tandem mass spectrometry, 2:719 Tangier disease, 2:1109–1112 TAR syndrome, 2:1112, 2:1112–1114 , 2:1114 Tay-Sachs disease, 2:1115–1116 amniocentesis, 1:75–76 carrier testing, 1:478 vs Niemann-Pick disease, 2:816 See also GM1-gangliosidosis Taybi, Hooshang, 2:1012 TBX5 gene, 1:559–561 T14484C mutation, 1:653–655 TCA cycle methylmalonic acidemia, 2:735–737 pyruvate dehydrogenase complex deficiency, 2:972–975 TCS (Treacher Collins syndrome), 2:1140–1142 Tedesco, T A., 1:448 Telescoping, alcoholism, 1:49 Telogen effluvium, 1:504–505 Tenting (Membranes), amniocentesis, 1:78 Teratogen, 2:1116–1119 accutane as, 1:11 alcohol, 1:423–424 amelia, 1:71 cerebral palsy, 1:214 holoprosencephaly, 1:557–558 list, 2:1118 phenylketonuria, 2:919–923 thalidomide, 2:1127 Testosterone congenital adrenal hyperplasia, 1:262, 265 male pattern hair loss, 1:504 Tetralogy of Fallot characteristics, 1:267 Cornelia de Lange syndrome, 1:280 frontonasal dysplasia, 1:441–442 Tetraploidy, 1:236 TGN (Thrombasthenia of Glanzmann and Naegli), 2:1133–1136 Thalassemia, 2:1119–1126 , 1123 classification, 2:1119 Thalidomide amelia, 1:71 embryopathy, 2:1127–1130 teratogenicity, 2:1117 therapeutic applications, 2:1127–1128 Thanatophoric dysplasia, 1:366, 1:368, 2:1130–1133 fibroblast growth factor receptor mutations, 1:429 short-rib polydactyly syndromes, 2:1044–1046 Thermotherapy, retinoblastoma, 2:994 Thiamine triphosphate, Leigh syndrome, 1:657 Thomson, Matthew S., 2:1010 Thoracopagus, conjoined twins, 1:273 Thrombasthenia of Glanzmann and Naegli (TGN), 2:1133–1136 Thrombocytopenia-absent radius syndrome, 2:1112, 2:1112–1114 , 2:1114 Thromboembolism, 1:405 Thrombosis, 1:405 Thymectomy, myasthenia gravis, 2:778–779 Thymus gland, accutane embryopathy and, 1:13 Thyroid gland congenital hypothyroid syndrome, 1:270–272 Pendred syndrome, 2:902–906 Thyroid releasing hormone, Pendred syndrome, 2:902–906 Thyroid stimulating hormone, congenital hypothyroid syndrome, 1:270–272 Thyrotropin-releasing hormone, congenital hypothyroid syndrome, 1:270–272 Thyroxine (T4) congenital hypothyroid syndrome, 1:270 Pendred syndrome, 2:902–906 Tiopronin, cystinuria, 1:307 Tissue non-specific alkaline phosphatase, 1:587–590 Tissue transplantation, 2:697, 699 Titmus II Vision Tester, 1:259 Tonsils, Tangier disease, 2:1111 TORCH test, 1:214 Torticollis, 1:640 Total anomalous pulmonary venous return, 1:267 Total craniosynostosis, 1:288 Tourette, Gilles de la, 2:1136 Tourette syndrome, 1:110, 2:1136–1140, 2: 1150 Toxoplasmosis, rubella, cytomegalovirus, and herpes test, 1:214 TPI (Triose phosphate isomerase deficiency), 2:1142–1144 Tracheoesophageal fistula Down syndrome, 1:349, 352 VATER association, 2:1169–1172 Tracheostomy, Treacher Collins syndrome, 2:1141 Traction alopecia, 1:504 Transcription factors, proto-oncogenes, 2:834 Transfer RNA (tRNA), 1:456, 2:1004–1005 GALE ENCYCLOPEDIA OF GENETIC DISORDERS Tris-hydroxymethyl aminomethane, Leigh syndrome, 1:658 Trisomy 8, 1:71 Trisomy 13 aneuploidy, 1:234 coloboma, 1:256 holoprosencephaly, 1:558 Patau syndrome, 2:890–893 Trisomy 18, 2:1144–1149 aneuploidy, 1:234 arthrogryposis multiplex congenita, 1:105 chromsome abnormalities, 2:1144–1145 coloboma, 1:256 distal arthrogryposis syndrome, 1:341 genetic counseling, 1:469 Trisomy 21 See Down syndrome Tritentine hydrochloride, Wilson disease, 2:1200–1201 tRNA Leu gene, 1:331 Truncus arteriosus, 1:112, 267 Trypsin gene, 1:543–546 TSC1 and genes, 2:1150 Tuberous sclerosis complex (TSC), 1:131, 2:1150–1154 , 1152 Tumor development, BeckwithWiedemann syndrome, 1:147–149 Tumor necrosis factor (TNF), gene therapy, 1:466 Tumor suppressor genes breast cancer genetics, 1:174 cancer genetics, 1:190 oncogene formation, 2:833–836 Tumors brain, 1:39, 665–666 desmoid, 1:192, 410–411 Wilms, 1:147–149, 2:1058 Turcot syndrome, 1:408 Turner, M F., 1:447 Turner-Kieser syndrome, 2:789–791 , 791 Turner syndrome, 2:1154–1156 , 1156 Duchenne muscular dystrophy, 1:362 hydrops fetalis, 1:580–581 sex chromosome aneuploidy, 1:235 Twin reversed arterial perfusion sequence, 1:7–9 Twin studies alcoholism genetics, 1:49 autism, 1:131 CHARGE syndrome, 1:223 multifactorial inheritance, 2:762 schizophrenia, 2:1024 Twin-twin transfusion syndrome, 1:7–9 Twins acardia, 1:8–9 conjoined, 1:272–274, 1:274 GALE ENCYCLOPEDIA OF GENETIC DISORDERS zygote formation, 2:1228 TWIST gene Carpenter syndrome, 1:206 craniosynostosis, 1:287, 289 Saethre-Chotzen syndrome, 1:106, 2:1019–1020 Type I diabetes See Insulin-dependent diabetes mellitus Type II collagen, chondrosarcoma, 1:228 Type II diabetes See Non-insulin dependent diabetes mellitus Tyrosinase-negative occulocutaneous albinism, 1:44–45 Tyrosine, alkaptonuria, 1:57 IU UBE3A gene, 1:92–93 UGT 1A1 gene, 2:1077 Ultrasound screening distal arthrogryposis syndrome, 1:341 Down syndrome, 1:351 Ellis-van Creveld syndrome, 1:382 encephalocele, 1:388 endoscopic, 2:1102 hemihypertrophy, 1:517 hydrolethalus syndrome, 1:578–579 Neu-Laxova syndrome, 2:799 oligohydramnios sequence, 2:829–830 Pfeiffer syndrome, 2:916–917 spina bifida, 2:1080–1081 transrectal, 1:195, 2:959 transvaginal, 1:195 trisomy 18, 2:1147–1148 Undifferentiated schizophrenia, 2:1023–1024 Unicoronal craniosynostosis, 1:288 Uniparental disomy Angelman syndrome, 1:92 Prader-Willi syndrome, 2:946 University of Washington, 1:565–566 Upper GI x ray, stomach cancer, 2:1101 Urea cycle disorders, 2:1159–1160 Apert syndrome, 1:100 ariginase deficiency, 1:101–102 ornithine transcarbamylase deficiency, 2:848–849 Urethritis, 1:94, 96 Uridyl diphosphogalactose-4epimerase, galactosemia III, 1:451 Urinalysis congenital adrenal hyperplasia, 1:263 galactosialodosis, 2:810 Hurler syndrome, 1:573–574 1343 Index Transforming growth factor-beta gene, 1:390 Transgenic experiment, alcoholism, 1:49–50 Transglutaminase-1 gene, 1:598–599 Translocation chromosome structural alteration, 1:236 gene mutation, 1:458–459 Prader-Willi syndrome, 2:946 Transplantation bone marrow (See Bone marrow transplantation) liver, 1:680, 2:849–850 lung, 1:300–301 organ, 1:304, 2:697, 699 peripheral stem cell, 1:197–198 tissue, 2:697, 699 Transposition of the great arteries asplenia, 1:112 characteristics, 1:267 Transrectal ultrasound defined, 1:195 prostate cancer, 2:959 Transvaginal ultrasound, 1:195 Treacher Collins syndrome (TCS), 2:1140–1142 Triamcinolone acetonide, hair loss treatment, 1:508 Tricho-dento-osseous syndrome, 1:373–374 Tricho-rhino-phalangeal syndrome II, 1:236, 1:645–646 Trichothiodystrophy, 2:1211 Trichotillomania, 1:504, 506–507 Tricuspid atresia, 1:267 Tricyclic antidepressants Asperger syndrome, 1:111 depression management, 1:327 hair loss treatment, 1:508 panic disorder, 2:883 Triglycerides, abetalipoproteinemia, 1:6 Triiodothyronine (T3) congenital hypothyroid syndrome, 1:270 Pendred syndrome, 2:902–906 Trinucleotide sequence Azorean disease, 1:135 fragile X syndrome, 1:431–433 Friedreich ataxia, 1:439–440 myotonic dystrophy, 2:785–788 spinocerebellar ataxia, 2:1084 Triose phosphate isomerase deficiency, 2:1142–1144 , 1144 Triphalangeal thumbs, Aase syndrome, 1:3–4 Triple X syndrome, 1:235 Triploidy, 1:235–236 Index Urinalysis (cont’d) neuraminidase deficiency, 2:806 polycystic kidney disease, 2:933–934 Urine, alkaptonuria and color of, 1:55–60 Uroporphyrinogen decarboxylase, 2:941–942 Uroporphyrinogen III cosynthase gene, 2:941 Usher syndrome, 2:1160–1165 , 1164 characteristics, 2:1160–1162 variants, 2:1162–1163 Uveitis, 1:94 IV Vaccines, diphtheria-pertussis-tetanus, 2:719–720 VACTERL association, 1:225, 2:1169–1172 Vagal nerve stimulation, epilepsy, 1:396 Valine, prion diseases, 2:950–952 Valium, cerebral palsy, 1:217 Valproic acid, bipolar disorder type II, 1:162 van der Burgt, Ineke, 2:819 Van der Knapp syndrome, 1:664 Van der Woude syndrome (VWS), 2:1167–1169 Variable expression Adams-Oliver syndrome, 1:34 branchiootorenal syndrome, 1:171 inheritance patterns, 1:611 Marfan syndrome, 2:707 Variegate porphyria, 2:940, 942 Vascular Ehlers-Danlos syndrome, 1:378 Vaso-occlusive events, sickle cell disease, 2:1050–1051 Vasopressin-2-receptor, nephrogenic diabetes insipidus, 2:794 VATER association, 1:225, 2:1169–1172 Velocardiofacial syndrome See Deletion 22q11 syndrome Venous switch, congenital heart defects, 1:269 Venter, J Craig, 1:566 Ventricular septal defect Aase syndrome, 1:4 asplenia, 1:112 characteristics, 1:267 Cornelia de Lange syndrome, 1:279 Holt-Oram syndrome, 1:560–561 Verma-Naumoff type SRPS, 1:382–383, 2:1045 1344 Very long chain fatty acids, adrenoleukodystrophy, 1:35–38 Vestibular areflexia, Usher syndrome type I, 2:1162 VHL (Von Hippel-Lindau syndrome), 2:1172–1177 Vineland Adaptive Behavior Scale, 1:424 Viral vectors, gene therapy, 1:464 Vision problems Aicardi syndrome, 1:40 albinism disorders, 1:45 Bardet-Biedl syndrome, 1:138 coloboma, 1:255–257 color blindness, 1:257–259 corneal dystrophies, 1:275–277 Fraser syndrome, 1:434–436 glaucoma, 1:484–487 Hermansky-Pudlak syndrome, 1:550–551 Leber congenital amaurosis, 1:649–652 Lebers hereditary optic atrophy, 1:652–655 macular degeneration, 2:691–695 Marfan syndrome, 2:711 myopia, 2:780–784 pseudoxanthoma elasticum, 2:967 See also Blindness Vitamin A, accutane embryopathy, 1:10 Vitamin B7, 2:720, 740, 845 Vitamin B6 therapy See Pyridoxine therapy Vitamin C alkaptonuria management, 1:60 Ehlers-Danlos syndrome, 1:380 Vitamin D hypophosphatemia, 1:591–593 osteoporosis, 2:862 Vitamin D receptor gene, 2:860–863 Vitamin deficiency, abetalipoproteinemia, 1:6 Vitamins Batten disease management, 1:140–141 cystinosis, 1:304 See also specific vitamins Vocal tics, 2:1137 von Hippel, Eugen, 2:1173 Von Hippel-Lindau syndrome, 2:1172–1177 , 1174 Von Recklinghausen disease See Neurofibromatosis von Rothmund, August, 2:1010 von Willebrand, Erik, 2:1177 Von Willebrand disease (VWD), 2:1177–1181 , 1180 hemophilia, 1:525–526 Noonan syndrome, 2:821 vs Osler-Weber-Rendu syndrome, 2:852 VSD See Ventricular septal defect VWD See Von Willebrand disease vWF factor, 2:1177–1181 VWS (Van der Woude syndrome), 2:1167–1169 IW Waardenburg, Petrus, 2:1183 Waardenburg Consortium, 2:1185 Waardenburg syndrome (WS), 2:1183–1187 , 1186 Walker-Warburg syndrome, 2:1187–1188 WAS (Wiskott-Aldrich syndrome), 2:1202–1205 , 1204 Watchful waiting, prostate cancer, 2:960 Water deprivation test, nephrogenic diabetes insipidus, 2:796 Watson, James, 1:343–344, 467 Watson-Schwartz test, 2:942–943 Watson syndrome, 2:821 Weaver, David, 2:1189 Weaver syndrome, 2:715–716, 2:1189–1190 Weight management, 1:2 Weissenbacher-Zweymuller syndrome (WZS), 2:1190–1192 Werdnig-Hoffmann disease, 2:1082 Wermer syndrome, 2:763–767 Werner, C W Otto, 2:1193 Werner syndrome, 1:248, 2:1193–1195 , 1194 Weyers acrofacial dysostosis, 1:381–383 Whistling face syndrome, 1:437–438, 2:1030 White blood cell testing, cystinosis, 1:303 Whitehead Institute for Medical Research, 1:565–566 Wiedemann, Hans Rudolf, 2:961 Wiedemann-Beckwith syndrome See Beckwith-Wiedemann syndrome Wildervanck syndrome, 1:356 Wilkins, Maurice, 1:344 Williams, J C P., 2:1195 Williams syndrome, 2:1195–1198 Wilms tumor Beckwith-Wiedemann syndrome, 1:147–149 Simpson-Golabi-Behmel syndrome, 2:1058 GALE ENCYCLOPEDIA OF GENETIC DISORDERS IX X chromosome Aarskog syndrome, 1:1–2 adrenoleukodystrophy gene, 1:35–36 albinism disorders, 1:45 asplenia, 1:112–113 Bruton agammaglobulinemia, 1:178–179 carrier testing, 1:477–478 choroideremia, 1:230 Coffin-Lowry syndrome, 1:249 color blindness, 1:257 Duchenne muscular dystrophy, 1:360, 362 Fabry disease, 1:401 FG syndrome, 1:426–427 fragile X syndrome, 1:430–431 gene structure, 1:456 hemophilia, 1:524–525 hermaphroditism, 1:552–553 Hunter syndrome, 1:568 hypophosphatemia, 1:592 ichthyosis, 1:597–599 Klinefelter syndrome, 1:636–638 Opitz syndrome, 2:837–838 sex chromosome aneuploidy, 1:234–235 sex-linked inheritance, 1:607–610, 1:610 Simpson-Golabi-Behmel syndrome, 2:1056 Turner syndrome, 2:1155–1156 X-linked agammaglobulinemia, 1:178–181 X-linked arthrogryposis, 1:106 X-linked dominant inheritance, 1:607–609 X-linked hereditary bullous dystrophy, 2:988 X-linked hydrocephaly, 2:1214–1218 , 1216 X-linked hypophosphatemia, 1:591–593 X-linked inheritance Aarskog syndrome, 1:2 amelia, 1:71–72 androgen insensitivity syndrome, 1:84 Charcot-Marie-Tooth disease, 1:220 Ehlers-Danlos syndrome, 1:376, 379 Emery-Dreifuss muscular dystrophy, 1:384–385 fragile X syndrome, 1:432 genetic disorders, 1:473–474 incontinentia pigmenti, 1:600–603 Leigh syndrome, 1:655–656 nephrogenic diabetes insipidus, 2:794–796 Opitz syndrome, 2:838 otopalatodigital syndrome, 2:863–865 Pelizaeus-Merzbacher disease, 2:899–900 Rett syndrome, 2:995 sideroblastic X-linked anemia, 1:87–89 Smith-Fineman-Myers syndrome, 2:1064–1065 X-linked mental retardation syndromes Renpenning syndrome, 2:987–989 Sutherland-Haan syndrome, 2:1105–1107 X-linked ocular albinism, 1:44 X-linked recessive inheritance adrenoleukodystrophy, 1:36–38 characteristics, 1:609 Kallman syndrome, 1:628 Kennedy disease, 1:635 Menkes syndrome, 2:729–730 Norrie disease, 2:822–823 ornithine transcarbamylase deficiency, 2:847–848 pedigree analysis, 2:898–899 GALE ENCYCLOPEDIA OF GENETIC DISORDERS severe combined immunodeficiency, 2:1042–1043 Simpson-Golabi-Behmel syndrome, 2:1056–1057 X-linked recessive retinitis pigmentosa, 2:990 X-linked semi-dominant inheritance, 1:609–610 X-linked sideroblastic anemia See Anemia, sideroblastic X-linked X-linked tetra-amelia, 1:70 X-ray crystallography, DNA structure, 1:344 X-ray examinations alkaptonuria, 1:59 chondrosarcoma, 1:228 hypophosphatasia, 1:589–590 osteoarthritis, 2:855–856 osteogenesis imperfecta, 2:858–859 prostate cancer, 2:959 stomach cancer, 2:1101–1102 Weaver syndrome, 2:1189–1190 Xeroderma pigmentosum, 1:248, 2:1211–1214 , 1212–1213 XLIS mutations, 1:676 Xp22.3 locus, 1:39–40 XX male syndrome, 2:1218–1221 , 1220 XYY syndrome, 2:1221–1223 IY Y chromosome gene structure, 1:456 hermaphroditism, 1:552–553 sex chromosome aneuploidy, 1:234–235 sex determining region Y, 2:1091–1093 sex-linked inheritance, 1:607–610, 1:610 IZ Z-DNA, 1:344 Zellweger, Hans, 2:1225 Zellweger syndrome, 2:1225–1227 Zinc supplement, Wilson disease, 2:1201 Zygote, 1:232, 2:1227–1230 , 1229 1345 Index Wilson disease, 2:1198–1201 , 1200–1201 dystonia, 1:370 sideroblastic X-linked anemia, 1:88 Windmill vane hand syndrome, 1:437–438, 2: 1030 Wireless endoscopy, hereditary colorectal cancer, 1:533 Wiskott, A., 2:1202 Wiskott-Aldrich syndrome (WAS), 2:1202–1205 , 1204 Witkop syndrome, 1:373 Wolf-Hirschhorn syndrome, 2:1205–1208 chromosomal deletions, 1:236 karyotype, 1:634 Wolman disease, 2:1208–1210 Woody Guthrie disease See Huntington disease World Health Organization, alpha-1 antitrypsin, 1:64 WRN gene, 2:1193–1194 WZS (Weissenbacher-Zweymuller syndrome), 2:1190–1192 ... and ethnic groups The rate of mutation of the fibrillin gene, however, appears to be related to the age of the patient’s GALE ENCYCLOPEDIA OF GENETIC DISORDERS father; older fathers are more likely.. .The GALE ENCYCLOPEDIA of Genetic Disorders VOLUME M-Z APPENDIX GLOSSARY INDEX S TAC E Y L B L AC H F O R D, E D I TO R The GALE ENCYCLOPEDIA of GENETIC DISORDERS STAFF Stacey... urine test In other cases, the diagnosis remains uncertain because of the mildness of the patient’s symptoms, the absence of a family history of the syndrome, and other variables These borderline