$Unique_ID{BRK04070} $Pretitle{} $Title{Osteogenesis Imperfecta} $Subject{Osteogenesis Imperfecta Brittle Bone Disease Ekman-Lobstein Disease Lobstein Disease (Type I) OI Osteopathyrosis Vrolik Disease (Type II) Osteogenesis Imperfecta Congenita also known as IO Congenita Osteoporosis Vitamin Resistant Rickets Achondroplasia Osteogenesis Imperfecta Tarda also knows as IO Tarda} $Volume{} $Log{} Copyright (C) 1984, 1985, 1986, 1987, 1988, 1990, 1992 National Organization for Rare Disorders, Inc. 16: Osteogenesis Imperfecta ** IMPORTANT ** It is possible that the main title of the article (Osteogenesis) Imperfecta is not the name you expected. Please check the SYNONYMS listing to find the alternate name and disorder subdivisions covered by this article. Synonyms Brittle Bone Disease Ekman-Lobstein Disease Lobstein Disease (Type I) OI Osteopathyrosis Vrolik Disease (Type II) DISORDER SUBDIVISIONS: Osteogenesis Imperfecta Congenita also known as IO Congenita Osteogenesis Imperfecta Tarda also knows as IO Tarda Information on the following diseases can be found in the Related Disorders section of this report: Osteoporosis Vitamin Resistant Rickets Achondroplasia General Discussion ** REMINDER ** The Information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Osteogenesis Imperfecta is characterized by unusually fragile bones that break or fracture easily. There are generally considered to be 4 types of this disorder, some with subtypes. The congenital form, type II, is the most severe; affected infants are either stillborn or die shortly after birth of respiratory insufficiency. Other forms of Osteogenesis Imperfecta range from mild to severe. Symptoms Osteogenesis Imperfecta is characterized by bone fractures, especially of the long bones of the legs, even after minimal trauma. Type I Osteogenesis Imperfecta is characterized by blue coloration to the membrane covering the rear portion of the eye (sclera). Generally there is little or no bone deformity and normal stature. There is hearing loss in about 50 percent of type I Osteogenesis Imperfecta patients. Type II Osteogenesis Imperfecta is lethal in the newborn period. Infants are born with multiple fractures as well as compressed fractures. Long bone deformities are generally present. Patients with type III Osteogenesis Imperfecta have short stature and only a variable bluish color to the sclera of the eye. Hearing loss and dental problems are common. Deformities of the bones tends to be progressive. Patients with type IV Osteogenesis Imperfecta have normal sclera in the eyes, mild bone deformity, and variable short stature. Abnormal development of dentin (a major component of the teeth, surrounding the pulp and covered with enamel) is also common (dentinogenesis). Hearing loss is rare. Causes Osteogenesis Imperfecta is commonly inherited as an autosomal dominant gene, but a recessive pattern has been identified in a few patients. More that 50 variants (mutations) in the genes that encode the chains of type I collagen have been identified. The exact nature of the mutation determines the type of Osteogenesis Imperfecta and the symptoms that are present. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In dominant disorders a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is fifty percent for each pregnancy regardless of the sex of the resulting child. In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If one receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is twenty-five percent. Fifty percent of their children will be carriers, but healthy as described above. Twenty-five percent of their children will receive both normal genes, one from each parent, and will be genetically normal. Affected Population Osteogenesis Imperfecta occurs in 1:20,000 to 1:50,000 births in the United States. Related Disorders Symptoms of the following disorders can be similar to Osteogenesis Imperfecta. Comparisons may be useful for a differential diagnosis: Osteoporosis is a disorder of the bones that is characterized by a decrease in the density and weight of bones (rarefaction). This can lead to fractures after even minor trauma. Osteoporosis occurs frequently in post- menopausal women or people that are immobile or sedentary. This disorder may cause pain, especially in the lower back, and a variety of deformities. Vitamin D Deficiency Rickets, which appears during infancy and childhood, is a disorder that is characterized by abnormal bone formation. Vitamin D is needed for the metabolism of calcium and phosphorus, which then affects the depositing of calcium in the bones. The major symptoms include restlessness and a lack of sleep, slow growth and there is a delay in crawling, sitting, or walking. If the disorder remains untreated, the ends of the long bones may become enlarged and the legs may bow. (For more information on this disorder, choose "Rickets, Vitamin D Deficiency" as your search term in the Rare Disease Database). Achondroplasia is a rare inherited disorder that results in short stature (dwarfism) due to the impairment of bone formation. Head and facial abnormalities are also associated with the disorder. Generally the characteristics include an unusually large forehead, short arms and legs, an elongated trunk, and hands that are short and broad. Water on the brain (hydrocephalus) may also be present and the compression of the brain stem may be fatal. (For more information on this disorder, choose "Achondroplasia" as your search term in the Rare Disease Database). Therapies: Standard The treatment for Osteogenesis Imperfecta is symptomatic and supportive. In the past treatments have included diets intended to promote calcium and magnesium deposition to the bone, and hormonal treatments with gonadotropins, growth hormone, and calcitonin. These have proven ineffective, and the latter in particular has had serious side effects on children. Exercise and physical therapy programs have proven of great value in strengthening muscles, increasing weight-bearing capacity, and reducing the tendency to fracture. Hydrotherapy (physical therapy in the water) has been particularly helpful. Various aids are also in use. "Rodding" is a standard procedure in which metal rods are surgically placed in the long bones to prevent fractures. Plastic braces are replacing plaster casts as protective devices because they permit greater freedom of movement and can be used in water. Inflatable suits can provide added protection, especially to very young children. Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive. Therapies: Investigational Research on birth defects and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of genetic disorders in the future. Resources For more information on Osteogenesis Imperfecta, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Osteogenesis Imperfecta Foundation 5000 W. Laurel St., Suite 210 Tampa, FL 33607-3836 (813) 282-1161 The National Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse Box AMS Bethesda, MD 20892 (301) 495-4484 Clinic: Dr. Michael P. White, Medical Director Metabolic Research Unit Shriners' Hospital for Crippled Children 2001 Lindbergh Blvd. Saint Louis, MO 63131 For genetic information and genetic counseling referrals, please contact: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References THE MERCK MANUAL 15th ed: R. Berkow, et al: eds; Merck, Sharp & Dohme Research Laboratories, 1987. Pp. 1948, 2104. CECIL TEXTBOOK OF MEDICINE, 18th ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Eds.: W.B. Saunders Co., 1988. Pp. 1180-1, 1982. MENDELIAN INHERITANCE IN MAN, 10th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1992. Pp. 1611-1614. CECIL TEXTBOOK OF MEDICINE, 19th Ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Editors; W.B. Saunders Co., 1990. Pp. 1124-1125. BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief; Blackwell Scientific Publications, 1990. Pp. 1321-1323. OSTEOGENESIS IMPERFECTA, P.H. Byers and R.D. Steiner; Annual Review Medicine (1992; 43): Pp. 269-282. OSTEOGENESIS IMPERFECTA, J.M. Gertner and L. Root; Orthop Clin North America (Jan. 1990; 21(1)): Pp. 151-162.