Thomson Gale 2002 Gale Encyclopedia of Genetic Disorders, Two Volume Set Volume 1 A L I pdf

  The GALE ENCYCLOPEDIA of

  

Genetic

Disorders

  The GALE ENCYCLOPEDIA of

  

Genetic

Disorders

S T A C E Y L . B L A C H F O R D , E D I T O R

  

V O L U M E

A-L

  

1

  The GALE ENCYCLOPEDIA of GENETIC DISORDERS

  7

  I. Blachford, Stacey. RB155.5 .G35 2001 616’.042’03—dc21

  1. Genetic disorders—Encyclopedias, Juvenile. [1. Genetic disorders—Encyclopedias. 2. Diseases—Encyclopedias.]

  ISBN 0-7876-5612-7 (set : hardcover : alk.paper

  1 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.

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  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

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  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

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CONTENTS

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . vii

Advisory Board . . . . . . . . . . . . . . . . . . . . . . xi

Contributors . . . . . . . . . . . . . . . . . . . . . . . . xiii

Entries

  Volume 1: A-L . . . . . . . . . . . . . . . . . . . . . .

  1 Volume 2: M-Z . . . . . . . . . . . . . . . . . . . . 691 Appendix Symbol Guide for Pedigree Charts . . . . . . 1231 Chromosome Map . . . . . . . . . . . . . . . . . 1233 Organizations List . . . . . . . . . . . . . . . . . 1241

  

Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . 1259

General Index . . . . . . . . . . . . . . . . . . . . . 1311 The Gale Encyclopedia of Genetic Disorders is a medical reference product designed to inform and educate readers about a wide variety of disorders, conditions, treatments, and diagnostic tests. Gale Group believes the product to be comprehensive, but not necessarily defini- tive. It is intended to supplement, not replace, consultation with a physician or other health care practitioner. While Gale Group has made substantial efforts to provide infor- mation that is accurate, comprehensive, and up-to-date, the Gale Group makes no representations or warranties of any kind, including without limitation, warranties of mer- chantability or fitness for a particular purpose, nor does it guarantee the accuracy, comprehensiveness, or timeliness of the information contained in this product. Readers should be aware that the universe of medical knowledge is constantly growing and changing, and that differences of medical opinion exist among authorities. They are also advised to seek professional diagnosis and treatment for any medical condition, and to discuss information obtained from this book with their health care provider.

  

PLEASE READ—IMPORTANT INFORMATION

  

INTRODUCTION

The Gale Encyclopedia of Genetic Disorders is a made up of seven medical and genetic experts, evaluated

unique and invaluable source for information regarding the topics and made suggestions for inclusion. Final

diseases and conditions of a genetic origin. This collec- selection of topics to include was made by the advisory

tion of nearly 400 entries provides in-depth coverage of board in conjunction with Gale Group editors. disorders ranging from exceedingly rare to very well- known. In addition, several non-disorder entries have

  been included to facilitate understanding of common The essays were compiled by experienced medical genetic concepts and practices such as Chromosomes, writers, primarily genetic counselors, physicians, and Genetic counseling, and Genetic testing. other health care professionals. The advisors reviewed This encyclopedia avoids medical jargon and uses the completed essays to insure they are appropriate, up- language that laypersons can understand, while still pro- to-date, and medically accurate. viding thorough coverage of each disorder medical pro- fessionals will find beneficial as well. The Gale Encyclopedia of Genetic Disorders fills a gap between HOW TO USE THIS BOOK basic consumer health resources, such as single-volume The Gale Encyclopedia of Genetic Disorders has family medical guides, and highly technical professional been designed with ready reference in mind. materials.

• Straight alphabetical arrangement of topics allows Each entry discussing a particular disorder follows a users to locate information quickly.

  standardized format that provides information at a Bold-faced terms direct the reader to related articles. • glance. The rubric used was:

Cross-references placed throughout the encyclopedia •

• Definition

  point readers to where information on subjects with-

• Description out entries may be found.
• Genetic pro>A list of key terms are provided where appropriate to
• Demographics define unfamiliar terms or concepts. Additional terms may be found in the glossary at the back of volume 2.
• Signs and symp>The Resources section directs readers to additional
• Diagnosis sources of medical information on a topic.
• Treatment and manage
• Valuable contact information for organizations and
• Prognosis

  support groups is included with each entry. The

• Resources

  appendix contains an extensive list of organizations arranged in alphabetical order.

• Key terms
• A comprehensive general index guides readers to all topics and persons mentioned in the text.

  A preliminary list of diseases and disorders was GRAPHICS compiled from a wide variety of sources, including pro-

fessional medical guides and textbooks, as well as con- The Gale Encyclopedia of Genetic Disorders con-

sumer guides and encyclopedias. The advisory board, tains over 200 full color illustrations, including photos and pedigree charts. A complete symbol guide for the pedigree charts can be found in the appendix.

  ACKNOWLEDGEMENTS The editor would like to thank the following individ- uals for their assistance with the Gale Encyclopedia of

  Reproduced by permission. Conjoined twins © Siebert/ Custom Medical Stock Photo. Reproduced by permis- sion. Corneal dystrophy © Gilman/Custom Medical Stock Photo. Reproduced by permission. Cystic fibrosis © 1992 Michael English, M. D. Custom Medical Stock Photo. Reproduced by permission. Depression © NIH/ Science Source, National Audubon Society Collection/ Photo Researchers, Inc. Reproduced with permission.

  Reproduced by permission. Karyotype © Science Photo Library/Custom Medical Stock Photo. Reproduced by permission. Liver cancer © CNRI/Photo Researchers, Inc. Reproduced by permission. McKusick-Kaufman syndrome © Thomas B. Hollyman, Science Source/

  © Bates/Custom Medical Stock Photo. Repro- duced by permission. Hydrocephalus © Lester V. Bergman/Corbis. Reproduced by permission. Ichthyosis © NMSB/Custom Medical Stock Photo. Reproduced by permission. Inheritance © Biophoto Associates/Photo Researchers, Inc. Reproduced by permission. Joubert syndrome © Gary Parker. SPL/Photo Researchers, Inc.

  /SPL/Custom Medical Stock Photo. Reproduced by per- mission. Gene therapy © Philippe Plailly. National Audubon Society Collection/Photo Researchers, Inc. Reproduced by permission. Genetic disorders © NMSB/ Custom Medical Stock Photo. Reproduced by permis- sion. Genetic testing © Phillippe Plailly. Science Photo Library, National Audubon Society Collection/Photo Researchers, Inc. Reproduced by permission. Glaucoma © 1995 Science Photo Library, Western Ophthalmic Hospital/Science Photo Library. Custom Medical Stock Photo. Reproduced by permission. Goltz syndrome © L I, Inc./Custom Medical Stock Photo. Reproduced by permission. Hair loss syndrome © NMSB/Custom Medical Stock Photo. Reproduced by permission. Hemo- philia

  Gene therapy © 1995, photograph by James King.

  Reproduced by permission. Fragile X syndrome © Siebert/Custom Medical Stock Photo. Reproduced by permission. Gene mapping © Sinclair Stammers. Photo Researchers, Inc. Reproduced by permission. Gene mutation © Joseph R. Siebert. Custom Medical Stock Photo. Reproduced by permission. Gene pool © Gerald Davis/Phototake NYC. Reproduced with permission.

  Reproduced by permission. Ehler-Danlos syndrome © NMSB/Custom Medical Stock Photo. Reproduced by permission. Encephalocele © Siebert/Custom Medical Stock Photo. Reproduced by permission. Epidermolysis bullosa © M. English/Custom Medical Stock Photo.

  Diabetes mellitus © 1992 Science Photo Library/ Custom Medical Stock Photo. Reproduced by permis- sion. Down syndrome © A. Sieveing. A. Sieveing/Petit Format/Photo Researchers, Inc. Reproduced by permis- sion. Dysplasia © Biophoto/Photo Researchers, Inc.

  Color blindness © Lester V. Bergman/Corbis. Repro- duced by permission. Congenital heart defects © Simon Fraser/Science Photo Library/Photo Researchers, Inc.

  Genetic Disorders : Deepti Babu, MS CGC, Dawn Jacob, MS, and Jennifer Neil, MS CGC, for the creation of the pedigree charts found in entries throughout the main body; K. Lee and Brenda Lerner for their assistance in compiling and reviewing most of the non-disorder entries in this encyclopedia; and to Connie Clyde, Kyung Kalasky, Beth Kapes, Monique Laberge, PhD, and Lisa Nielsen for their extensive assistance with the final phase of manuscript preparation.

  Reproduced with permission. Coloboma © P. Marazzi. SPL/Photo Researchers, Inc. Reproduced by permission.

  Cerebral palsy © Will McIntyre. W. McIntyre/Photo Researchers, Inc. Reproduced by permission. Chromo- somes © CNRI/Science Photo Library. Photo Researchers, Inc. Reproduced by permission. Cleft lip and palate © NMSB/Custom Medical Stock Photo. Reproduced by permission. Clubfoot © Science Source, National Audubon Society Collection/Photo Researchers, Inc.

  Reproduced by permission. Bicuspid aortic valve © Roseman/Custom Medical Stock Photo. Reproduced by permission. Cancer © Nina Lampen. Science Source/ Photo Researchers, Inc. Reproduced by permission.

  Reproduced by permission. Ankylosing spondylitis © P. Marazzi. SPL/Photo Researchers, Inc. Reproduced by permission. Apert syndrome © Ansary/Custom Med- ical Stock Photo. Reproduced by permission. Asthma © 1993 B. S. I. P. / Custom Medical Stock Photo. Repro- duced by permission. Attention deficit hyperactivity disorder © Robert J. Huffman. Field Mark Publications.

  Amniocentesis © Will and Demi McIntyre. National Audubon Society Collection/Photo Researchers, Inc.

  © David Frazier/Photo Researchers, Inc. Reproduced by permission. Acromegaly © NMSB/ Custom Medical Stock Photo. Reproduced by permis- sion. Albinism © Norman Lightfoot. National Audubon Society Collection/Photo Researchers, Inc. Reproduced by permission. Alzheimer disease © Alfred Pasieka. SPL/Photo Researchers, Inc. Reproduced by permission.

  All photographs and illustrations throughout the Gale Encyclopedia of Genetic Disorders have been reproduced by permission from the source noted in each caption. Special acknowledgement is given to the pho- tographers of photographs found in the following entries: Achondroplasia

  Introduction

  Photo Researchers. Reproduced by permission. Meckel diverticulum © 1991, photograph. NMSB/Custom Medical Stock Photo. Reproduced by permission. Nar- colepsy © Bannor/Custom Medical Stock Photo. Repro- duced by permission. Olser-Rendu-Weber syndrome © P. Marazzi. SPL/Photo Researchers, Inc. Reproduced by permission. Oral-facial-digital syndrome © Photog- raphy by Keith. Custom Medical Stock Photo. Repro- duced by permission. Osteogenesis imperfecta © Joseph Siebert, Ph. D. Custom Medical Stock Photo.

  Reproduced by permission. Osteoperosis © 1993 Patrick McDonnel. Custom Medical Stock Photo. Reproduced by permission. Otopalatodigital syndrome © Biophoto Associates/Science Source/Photo Researchers, Inc. Reproduced by permission. Pancreatic cancer © John Bavosi/Science Photo Library. Custom Medical Stock Photo. Reproduced by permission. Polycystic kidney disease © A. Glauberman. Photo Researchers, Inc. Reproduced by permission. Porphyrias © Ansary/ Custom Medical Stock Photo. Reproduced by permis- sion. Potter syndrome © Siebert/Custom Medical Stock Photo. Reproduced by permission. Progeria © NMSB/ Custom Medical Stock Photo. Reproduced by permis- sion. Prostate cancer © Dr. P. Marazzi. Photo Researchers, Inc. Reproduced by permission. Prune belly syndrome © Ansary/Custom Medical Stock Photo. Reproduced by permission. Raynaud disease © 1997, photograph. P. Stocklein/Custom Medical Stock Photo. Reproduced by permission. Retinitis pigmentosa © Sci- ence Photo Library/Custom Medical Stock Photo. Repro- duced by permission. Scleroderma © Dr. P. Marazzi. Photo Researchers, Inc. Reproduced by permission.

  Scoliosis © NMSB/Custom Medical Stock Photo. Repro- duced by permission. Sickle cell anemia © Dr. Gopal Murti. National Audubon Society Collection/Photo

  Researchers, Inc. Reproduced by permission. Sickle cell anemia © 1995 Science Photo Library. Custom Medical Stock Photo. Reproduced by permission. Spina bifida © Biophoto Associates, National Audubon Society Collection/Photo Researchers, Inc. Reproduced by per- mission. Stein-Leventhal syndrome © P. Marazzi. SPL/ Photo Researchers, Inc. Reproduced by permission.

  Stomach cancer © Science Photo Library/Custom Medical Stock Photo. Reproduced by permission. Sturge-Weber syndrome © Mehau Kulyk. SPL/Photo Researchers, Inc. Reproduced by permission. Suther- land-Haan syndrome © Biophoto Associates/Photo Researchers, Inc. Reproduced by permission. Tay-Sachs disease © 1992 IMS Creative/Graph/Photo. Custom Medical Stock Photo. Reproduced by permission. Thalassemia © John Bavosi. SPL/Photo Researchers, Inc. Reproduced by permission. Triose phosphate iso- merase © photograph. NMSB/Custom Medical Stock Photo. Reproduced by permission. Trisomy 13 © 1992 Ralph C. Eagle, M.D./Photo Researchers, Inc. Repro- duced by permission. Trisomy 18 © Department of Clin- ical Cytogenetics, Addenbrookes Hospital/Science Photo Library/Photo Researchers, Inc. Reproduced by permis- sion. Tuberous sclerosis © LI Inc./Custom Medical Stock Photo. Reproduced by permission. Turner syn- drome © NMSB/Custom Medical Stock Photo. Repro- duced by permission. Usher syndrome © L. Steinmark.

  Custom Medical Stock Photo. Reproduced by permis- sion. Werner syndrome © NMSB/Custom Medical Stock Photo. Reproduced by permission. Wilson disease © Science Photo Library/Photo Researchers, Inc. Repro- duced by permission. Zygote © Dr. Yorgos Nikas/ Science Photo Library/Photo Researchers, Inc. Repro- duced by permission.

  Introduction

ADVISORY BOARD

  Stephen Braddock, MD Assistant Professor Director, Missouri Teratogen Information Service

  (MOTIS) Division of Medical Genetics University of Missouri-Columbia School of

  Medicine Columbia, Missouri Cynthia R. Dolan, MS CGC Clinical Director/Genetic Counselor Inland Northwest Genetic Clinic Spokane, Washington Associate Editor GeneClinics: Clinical Genetics Information Resource University of Washington School of Medicine Seattle, Washington Laith Farid Gulli, MD MSc, MSc(MedSci), MSA, MscPsych, MRSNZ FRSH, FRIPHH, FAIC, FZS

  Consultant Psychotherapist in Private Practice Lathrup Village, Michigan Katherine Hunt, MS Senior Genetic Counselor/Lecturer School of Medicine University of New Mexico Albuquerqe, New Mexico Richard McCartney, MD Diplomat, American Board of Surgery Fellow, American College of Surgeons Richland, Washington William K. Scott, PhD Assistant Research Professor Center for Human Genetics Duke University Medical Center Durham, North Carolina Roger E. Stevenson, MD Director Greenwood Genetic Center Greenwood, South Carolina

  

An advisory board comprised of genetic specialists from a variety of backgrounds provided invaluable assistance in the for-

mulation of this encyclopedia. This advisory board performed a myriad of duties, from defining the scope of coverage to

reviewing individual entries for accuracy and accessibility. We would therefore like to express our sincere thanks and appre-

ciation for all of their contributions.

  Christine Adamec Medical Writer Palm Bay, FL Margaret Alic, PhD Science Writer Eastsound, WA Lisa Andres, MS CGC Certified Genetic Counselor Medical Writer San Jose, CA Greg Annussek Medical Writer/Editor New York, NY Sharon Aufox, MS CGC Genetic Counselor Rockford Memorial Hospital Rockford, IL Deepti Babu, MS Genetic Counselor Marshfield Clinic Marshfield, WI Kristin Baker Niendorf, MS CGC Genetic Counselor Massachusetts General Hospital Boston, MA Carin Lea Beltz, MS CGC Genetic Counselor and Program Director The Center for Genetic Counseling Indianapolis, IN Abdel Hakim Ben Nasr, PhD Medical Writer Dept. of Genetics Yale University School of

  Medicine New Haven, CT Tanya Bivins, BS Nursing Student Madonna University Livonia, MI Bethanne Black Medical Writer Atlanta, GA Jennifer Bojanowski, MS CGC Genetic Counselor Children’s Hospital Oakland Oakland, CA Shelly Q. Bosworth, MS CGC Genetic Counselor Eugene, OR Michelle L. Brandt Medical Writer San Francisco, CA Dawn Cardeiro, MS CGC Genetic Counselor Fairfield, PA Suzanne M. Carter, MS CGC Senior Genetic Counselor Clinical Coordinator Montefiore Medical Center Bronx, NY Pamela E. Cohen, MS CGC Genetic Counselor San Francisco, CA Randy Colby, MD Senior Medical Genetics Fellow Greenwood Genetic Center Greenwood, SC Sonja Eubanks, MS CGC Genetic Counselor Division of Maternal-Fetal Medicine

  University of North Carolina at Chapel Hill Chapel Hill, NC David B. Everman, MD Clinical Geneticist Greenwood Genetic Center Greenwood, SC L. Fleming Fallon, Jr., MD DrPH Associate Professor of Public Health Bowling Green State University Bowling Green, OH Antonio Farina, MD PhD Medical Writer Dept. of Embryology University of Bologna Italy Kathleen Fergus, MS Genetic Counselor/Medical Writer San Francisco, CA Lisa Fratt Medical Writer Ashland, WI Sallie B. Freeman, PhD Assistant Professor Dept. of Genetics Emory University Atlanta, GA Mary E. Freivogel, MS Account Executive Myriad Genetic Laboratories, Inc.

  Salt Lake City, UT Rebecca Frey, PhD Consulting Editor East Rock Institute Yale University New Haven, CT

  

CONTRIBUTORS Sandra Galeotti, MS Medical Writer Sau Paulo, Brazil Avis L. Gibons Genetic Counseling Intern UCI Medical Center Orange, CA Taria Greenberg, MHS Medical Writer Houston, TX David E. Greenberg, MD Medicine Resident Baylor College of Medicine Houston, TX Benjamin M. Greenberg Medical Student Baylor College of Medicine Houston, TX Farris Farid Gulli, MD Plastic and Reconstructive Surgery Farmington Hills, MI Judy C. Hawkins, MS Genetic Counselor The University of Texas Medical Branch Galveston, TX David Helwig Medical Writer London, ON, Canada Edward J. Hollox, PhD Medical Writer Institute of Genetics, Queen’s Medical Center University of Nottingham Nottingham, England Katherine S. Hunt, MS Genetic Counselor University of New Mexico Health Sciences Center Albuquerque, NM Cindy Hunter, MS CGC Genetic Counselor Medical Genetics Department Indiana University School of

  Medicine Indianapolis, IN Kevin Hwang, MD Medical Writer Morristown, NJ Holly A. Ishmael, MS CGC

  Genetic Counselor

The Children’s Mercy Hospital

Kansas City, MO Dawn A. Jacob, MS Genetic Counselor Obstetrix Medical Group of Texas Fort Worth, TX Paul A. Johnson Medical Writer San Diego, CA Melissa Knopper Medical Writer Chicago, IL Terri A. Knutel, MS CGC Genetic Counselor Chicago, IL Karen Krajewski, MS CGC Genetic Counselor

Assistant Professor of Neurology

Wayne State University Detroit, MI Sonya Kunkle Medical Writer Baltimore, MD Renée Laux, MS Certified Genetic Counselor

Eastern Virginia Medical School

Norfolk, VA Marshall Letcher, MA Science Writer Vancouver, BC Christian L. Lorson, PhD Assistant Professor Dept. of Biology Arizona State University Tempe, AZ Maureen Mahon, BSc MFS Medical Writer Calgary, AB Nicole Mallory, MS Medical Student Wayne State University Detroit, MI

Ron C. Michaelis, PhD FACMG

Research Scientist Greenwood Genetic Center Greenwood, SC

  Bilal Nasser, MSc Senior Medical Student Universidad Iberoamericana Santo Domingo, Domincan

  Republic Jennifer E. Neil, MS CGC Genetic Counselor Long Island, NY Pamela J. Nutting, MS CGC Senior Genetic Counselor Phoenix Genetics Program University of Arizona Phoenix, AZ Marianne F. O’Connor, MT

  (ASCP) MPH Medical Writer Farmington Hills, MI Barbara Pettersen, MS CGC Genetic Counselor Genetic Counseling of Central Oregon Bend, OR Toni Pollin, MS CGC Research Analyst Division of Endocrinology, Diabetes, and Nutrition University of Maryland School of Medicine Baltimore, MD Scott J. Polzin, MS CGC Medical Writer Buffalo Grove, IL Nada Quercia, Msc CCGC CGC Genetic Counselor Division of Clinical and Metabolic Genetics The Hospital for Sick Children Toronto, ON, Canada Robert Ramirez, BS Medical Student University of Medicine & Dentistry of New Jersey Stratford, NJ Julianne Remington Medical Writer Portland, OR Jennifer Roggenbuck, MS CGC Genetic Counselor Hennepin County Medical Center Minneapolis, MN

  Contributors

  Edward R. Rosick, DO MPH MS University Physician/Clinical Assistant Professor The Pennsylvania State University University Park, PA Judyth Sassoon, ARCS PhD Medical Writer Dept. of Chemistry and Biochemistry University of Bern Bern, Switzerland Jason S. Schliesser, DC Chiropractor Holland Chiropractic, Inc.

  Holland, OH Charles E. Schwartz, PhD Director of Center for Molecular Studies JC Self Research Center Greenwood Genetic Center Greenwood, SC Laurie H. Seaver, MD Clinical Geneticist Greenwood Genetic Center Greenwood, SC Nina B. Sherak, MS CHES Health Educator/Medical Writer Wilmington, DE Genevieve Slomski, PhD

  Medical Writer New Britain, CT Java O. Solis, MS Medical Writer Decatur, GA Amie Stanley, MS Genetic Counselor University of Florida Gainesville, FL Constance K. Stein, PhD Director of Cytogenetics Assistant Director of Molecular Diagnostics SUNY Upstate Medical University Syracuse, NY Kevin M. Sweet, MS CGC Cancer Genetic Counselor James Cancer Hospital Ohio State University Columbus, OH Catherine Tesla, MS CGC Senior Associate, Faculty Dept. of Pediatrics, Division of Medical Genetics Emory University School of Medicine Atlanta, GA Oren Traub, MD PhD

  Resident Physician Dept. of Internal Medicine University of Washington Affiliated

  Hospitals Seattle, WA Amy Vance, MS CGC Genetic Counselor GeneSage, Inc.

  San Francisco, CA Brian Veillette, BS Medical Writer Auburn Hills, MI Linnea E. Wahl, MS Medical Writer Berkeley, CA Ken R. Wells Freelance Writer Laguna Hills, CA Jennifer F. Wilson, MS Science Writer Haddonfield, NJ Philip J. Young, PhD Research Fellow Dept. of Biology Arizona State University Tempe, AZ Michael V. Zuck, PhD Medical Writer Boulder, CO

  Contributors

  

A

  Although the responsible gene has been identified, test-

  4p minus syndrome see Wolf-Hirschhorn

  ing for gene mutations is available only in research labo-

  syndrome

  ratories. Aarskog syndrome is also called Faciogenital dysplasia, Faciogenitodigital syndrome, and Aarskog-

  5p deletion syndrome see Cri du chat Scott syndrome. syndrome

Genetic profile

  5p minus syndrome see Cri du chat syndrome

  Aarskog syndrome is caused by mutations in the FGD1 gene, located on the short arm of the X chromo-

  

22q1 deletion syndrome see Deletion 22q1 some (Xp11.2). In most cases, the altered gene in

  affected males is inherited from a carrier mother. Since

  syndrome

  males have a single X chromosome, mutations in the FGD1 gene produces full expression in males. Females

  47,XXY syndrome see Klinefelter syndrome

  who carry a mutation of the FGD1 gene on one of their two X

  chromosomes are usually unaffected, but may

  have subtle facial differences and less height than other females in the family.

  Female carriers have a 50/50 chance of transmitting

Aarskog syndrome

  the altered gene to daughters and each son. Affected

Definition males are fully capable of reproduction. They transmit

  their single X chromosome to all daughters who, there- Aarskog syndrome is an inherited disorder that fore, are carriers. Since males do not transmit their single causes a distinctive appearance of the face, skeleton, X chromosome to sons, all sons are unaffected. hands and feet, and genitals. First described in a Norwegian family in 1970 by the pediatrician Dagfinn

  The gene affected in Aarskog FGD1 codes for a Aarskog, the disorder has been recognized worldwide in

  Rho/Rac guanine exchange factor. While the gene prod- most ethnic and racial groups. Because the responsible uct is complex and the details of its function are incom-

  

gene is located on the X chromosome, Aarskog syn- pletely understood, it appears responsible for conveying

  drome is manifest almost exclusively in males. The messages within cells that influence their internal archi- prevalence is not known. tecture and the activity of specific signal pathways.

  However, the precise way in which mutations in FGD1 produce changes in facial appearance and in the skeletal

  Description and genital systems is not yet known.

  Aarskog syndrome is among the

  genetic disorders

  with distinctive patterns of physical findings and is con-

Demographics

  fused with few others. Manifestations are present at birth allowing for early identification. The facial appearance Only males are affected with Aarskog syndrome, and findings in the skeletal system and genitals combine although carrier females may have subtle changes of the to make a recognizable pattern. The diagnosis is almost facial structures and be shorter than noncarrier sisters. exclusively based on recognition of these findings. There are no high risk racial or ethnic groups. association with behavioral disturbances. However, attention deficit occurs among some boys with learning difficulties.

  The diagnosis of Aarskog syndrome is made on the basis of clinical findings, primarily analysis of the family history and characteristic facial, skeletal, and genital findings. There are no laboratory or radi- ographic changes that are specific. Although the diag- nosis can be confirmed by finding a mutation in the FGD1 gene, this type of testing is available only in research laboratories.

  In families with a prior occurrence of Aarskog syn- drome, prenatal diagnosis might be possible through ultrasound examination of the face, hands, and feet, or by testing the FGD1 gene. However, this is not generally sought since the condition is not considered medically severe.

  Although most affected males have normal intellec- tual function, some individuals will have mild impair- ments. There does not appear to be any particular

  Changes in the appearance of the genitals may also be helpful in diagnosis. One or both testes may remain in the abdomen, rather than descending into the scrotal sac. The scrotum tends to surround the penis giving a so- called “shawl scrotum” appearance. Hernias may appear in the genital and umbilical regions. Linear growth in childhood and adult height are generally less than in unaffected brothers. The head size is usually normal.

  The fingers are often held in a distinctive position with flexion at the joint between the hand and the fin- gers, over extension at the first joint of the finger and flexion at the second joint. This hand posturing becomes more obvious when there is an attempt to spread the fingers. There may also be some mild web- bing between the fingers. The fingers are short and there is often only a single crease across the middle of the palm. The toes are also short and the foot is often bent inward at its middle portion. All of the joints may be unusually loose. Excessive movement of the cervical spine may lead to impingement on the spinal cord. In some cases, the sternum (breastbone) may appear depressed (pectus excavatum).

  Manifestations of Aarskog syndrome are present from birth. The facial appearance is distinctive and in most cases is diagnostic. Changes are present in the upper, middle, and lower portion of the face. Increased width of the forehead, growth of scalp hair into the mid- dle of the forehead (widow’s peak), increased space between the eyes (ocular hypertelorism), a downward slant to the eye openings, and drooping of the upper eye- lids (ptosis) are the major features in the upper part of the face. A short nose with forward-directed nostrils and sim- ply formed small ears that may protrude are the major findings in the mid-part of the face. The mouth is wide and the chin small. As the face elongates in adult life, the prominence of the forehead and the increased space between the eyes becomes less apparent. Dental abnor- malities include slow eruption, missing teeth, and broad upper incisors.

  class of proteins that appear to convey signals important in the structure and biochemical activity of cells.

  Rho/Rac guanine exchange factor—Member of a

Diagnosis

Aarskog syndrome KEY TERMS

Signs and symptoms

  Life threatening malformations or other health concerns rarely occur. Special educational attention may be neces- sary for those with learning difficulties. A minority of affected persons will have spinal cord compression, usu-

  Prognosis Short-term and long-term prognosis is favorable.

  The X-linked inheritance pattern should be described to the family.

  Since there are no major malformations or major mental disabilities in Aarskog syndrome, the diagnosis may be reassuring. Developmental milestones and school progress should be monitored, as there may be impair- ment of intellectual function in some individuals.

  As in many disorders, there is a range of severity of the clinical appearance even within the same family. In these cases, examination of several affected family mem- bers and attention to family history may be helpful.

  The older patient may pose greater difficulty due to loss of facial findings and obscuring of shawl scrotum by pubic hair.

  Few other conditions are confused with Aarskog syndrome. Noonan syndrome, another single gene dis- order that has short stature, ocular hypertelorism, downslanting eye openings, and depression of the lower chest, poses the greatest diagnostic confusion. Patients with Noonan syndrome often have wide necks and heart defects, which is helpful in distinguishing them from patients with Aarskog syndrome.

Treatment and management

Aase syndrome Aarskog Syndrome

  Aarskog, D. “A familial syndrome of short stature associated with facial dysplasia and genital anomalies.” Journal of Pediatric Medicine 77 (1971): 856.

  Wide spaced eyes Broad forehead (Gale Group)

  Undescended testes at birth 2mos 2y Shawl scrotum

  Shawl scrotum Inguinal hernia (repaired) Attention deficit

  67y 5'11" Learning disabilities

  43y 5'3" Webbed fingers Broad thumbs

  39y 5'7" 37y 5'4" Widows peak Short fingers

  44y 6'1" 40y 5'10"

  ally in the neck, causing pain or injury to peripheral nerves. Neurosurgical intervention is necessary in some cases. Hernias in the umbilical and groin areas may be surgically repaired.

  19y 5'5" 15y 5'9"

  d.34y in accident "slow"

d.55y

Lung cancer

5' 2"

Webbed fingers

Ptosis

I Aase syndrome Definition

Resources PERIODICALS

  Aase syndrome is sometimes also called Aase–Smith syndrome, or Congenital Anemia–Triphalangeal Thumb syndrome. It is a very rare hereditary syndrome involving multiple birth defects. The two symptoms that must be present to consider the diagnosis of Aase syndrome are CHA and TPT. CHA is a significant reduction from birth in the number of red cells in the blood. TPT means that one or both thumbs have three bones (phalanges) rather than the normal two.

  Aase syndrome is a rare, autosomal recessive genetic disorder characterized by congenital hypoplastic anemia (CHA) and triphalangeal thumbs (TPT). People with Aase syndrome may have one or more physical abnor- malities. Poor growth in childhood is common, but men- tal retardation and other neurological problems are not associated with Aase syndrome.

  Roger E. Stevenson, MD

  (800) 999-6673. Fax: (203) 746-6481. ⬍http://www .rarediseases.org⬎.

  NW, Suite 404, Washington, DC 20008. (202) 966-5557. Fax: (202) 966-8553. ⬍http://www.geneticalliance.org⬎. National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or

  ORGANIZATIONS Alliance of Genetic Support Groups. 4301 Connecticut Ave.

  Pasteris, N. G., et al. “Isolated and characterization of the facio- genital dysplasia (Aarskog-Scott syndrome) gene: A puta- tive Rho/Rac guanine nucleotide exchange factor.” Cell 79 (1994): 669.

  14y 5'4" 9y 4'6"

Description

  mal gene proven to cause Aase syndrome had not been discovered.

Demographics

Aase syndrome KEY TERMS

  Aase syndrome is quite rare, with possibly no more than two dozen cases reported in the medical literature.

Signs and symptoms

  Autosomal recessive inheritance is suspected for Aase syndrome based on the pattern seen in the families that have been described. An autosomal recessive pattern requires that only siblings are affected by the condition (parents are unaffected gene carriers), and the disorder occurs equally in males and females. As of 2000, an abnor-

  The available evidence suggests Aase syndrome is inherited in an autosomal recessive fashion meaning that an affected person has two copies of an abnormal gene. Parents of an affected individual carry one abnormal copy of that particular gene, but their other gene of the pair is normal. One copy of the normal gene is sufficient for the parent to be unaffected. If both parents are carri- ers of a gene for the same autosomal recessive condition, there is a one in four chance in each pregnancy that they will both pass on the abnormal gene and have an affected child.

  Several other physical abnormalities have been described in individuals with Aase syndrome, including narrow shoulders, hypoplastic radius (underdevelopment of one of the bones of the lower arm), heart defect, cleft lip/palate, and late closure of the fontanelles (soft spots on an infant’s skull where the bones have not yet fused). The specific cause of Aase syndrome is not known, but recurrence of the condition in siblings implies an abnor- mal gene is responsible.

  Hypoplastic radius—Underdevelopment of the radius, the outer, shorter bone of the forearm.

  skull where the developing bones of the skull have yet to fuse.

  Fontanelle—One of several “soft spots” on the

  cant reduction in the number of red blood cells present at birth, usually referring to deficient pro- duction of these cells in the bone marrow. Also sometimes called congenital aplastic anemia.

  Congenital hypoplastic anemia (CHA)—A signifi-

  with congenital hypoplastic anemia. Some researchers believe that some or all individuals with Aase syndrome actually have BDS, that Aase syndrome and BDS are not separate disorders.

  Blackfan-Diamond syndrome (BDS)—A disorder

  Anemia associated with Aase syndrome is often helped by the use of a steroid medication. For serious anemia that does not respond to medications, blood trans- fusions from a matched donor might be necessary. Management of problems related to the skeletal abnor- malities should be treated by orthopedic surgery as well as physical and occupational therapy. Heart defects and cleft lip and palate are nearly always correctable, but both require surgery and long–term follow up. A genetic eval- uation and counseling should be offered to any individual

  The diagnosis of Aase syndrome is made when an infant has CHA and TPT, and one or more of the other symptoms. Children with another more common congen- ital anemia syndrome, Blackfan–Diamond syndrome (BDS), sometimes have abnormalities of their thumbs. Since the syndromes have overlapping symptoms, there is some question about whether Aase syndrome and BDS are contiguous gene syndromes or even identical condi- tions. Further genetic research may resolve this issue.

  Slow growth in children with Aase syndrome may be partly related to their anemia, but is more likely to be genetically predetermined due to the syndrome. Ventricular septal defect (VSD), a hole between the bot- tom two chambers of the heart, is the cardiac defect reported most often, and several cases of cleft lip and palate have occurred as well.

  CHA and TPT are the two classic signs of Aase syn- drome. The anemia may require treatment with steroids, or possibly blood transfusions, but tends to improve over time. TPT may cause a person with Aase syndrome to have difficulty grasping and manipulating objects with their hands. A hypoplastic radius may complicate prob- lems with appearance and movement of the hands and arms. Narrow and sloping shoulders are caused by abnormal development of the bones in that area of the body.

Triphalangeal thumb (TPT)—A thumb that has three bones rather than two

Diagnosis

Genetic profile

Treatment and management

  or couple whose child is suspected of having Aase syndrome.

Prognosis

Description

  While major medical procedures such as blood transfusions and corrective surgeries might be needed for a child with Aase syndrome, the long–term prognosis seems to be good. Discovery of the specific genetic defect is not likely to immediately change the prognosis. Development of a reliable genetic test, however, might allow for carrier testing for other family members, and prenatal diagnosis for couples who already have an affected child.

  Abetalipoproteinemia

  ABL is rare, and the true incidence of the disorder is unknown. Prior to the description of ABL in 1950, it is

  ABL is an autosomal recessive genetic disorder. This means that both copies of the MTP gene are abnormal in a person affected with the disorder. Since all genes are present at conception, a person cannot “acquire” ABL. Each parent of an affected child carries the abnormal MTP gene but also has a normally functioning gene of that pair. Enough functional MTP is produced by the nor- mal gene so that the parent is unaffected (carrier). When both parents are carriers of the same recessive gene, there is a one in four chance in each pregnancy that they will have an affected child.

  Fats are important components of a normal diet, and their processing, transport, and use by the body are criti- cal to normal functioning. Lipids bind to protein (lipoprotein) so they can be absorbed in the intestine, transferred through the blood, and taken up by cells and tissues throughout the body. There are many different lipoprotein complexes in the body. One group, the betal- ipoproteins, must combine with another protein, micro- somal triglyceride transfer protein (MTP). ABL is caused by abnormalities in the gene that codes for MTP. When MTP is nonfunctional or missing, then betalipoproteins will also be decreased or absent. The MTP gene has been localized to chromosome 4.

  The underlying problem in ABL is a difficulty in absorbing fats (lipids) in the intestine. Most people with ABL first develop chronic digestive problems, and then progress to neurological, muscular, skeletal, and ocular disease. Disorders of the blood may also be present. Severe vitamin deficiency causes many of the symptoms in ABL. Treatments include restricting fat intake in the diet and vitamin supplementation. Even with early diag- nosis and treatment, though, ABL is progressive and can- not be cured.