$Unique_ID{BRK03892} $Pretitle{} $Title{Kallmann Syndrome} $Subject{Kallmann Syndrome Hypogonadism with Anosmia Hypogonadotropic Hypogonadism and Anosmia Klinefelter Syndrome Noonan Syndrome Turner Syndrome} $Volume{} $Log{} Copyright (C) 1991, 1992 National Organization for Rare Disorders, Inc. 848: Kallmann Syndrome ** IMPORTANT ** It is possible that the main title of the article (Kallmann Syndrome) is not the name you expected. Please check the SYNONYM listing to find the alternate name and disorder subdivisions covered by this article. Synonyms Hypogonadism with Anosmia Hypogonadotropic Hypogonadism and Anosmia Information on the following diseases can be found in the Related Disorders section of this report: Klinefelter Syndrome Noonan Syndrome Turner Syndrome 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. Kallmann Syndrome is a rare inherited disorder in which the organ that produces sex cells does not function properly (hypogonadism) and there is a loss of the sense of smell (anosmia). The impaired production of hormones as well as sperm and egg cells often causes delayed puberty, growth and infertility. This disorder affects both males and females , although it is more common in males. Symptoms Kallmann Syndrome consists of a combination of symptoms. The ovaries in females and testes in males (known as gonadal glands) do not function properly causing retardation of growth and sexual development. A impaired sense of smell (anosmia ) also occurs. Other symptoms of this disorder may include delayed puberty, color blindness, cleft-lip or palate, hearing loss and abnormal or absent kidney development (renal agenesis). In more severe forms of Kallmann Syndrome abnormalities of the skeleton such as webbing of two or more fingers or toes (syndactyly), a short fourth finger of the hand, mental retardation, or an absence of symmetry in the skull and face (craniofacial asymmetry) may occur. Females with this disorder may have a deficiency in estrogen (a female sex hormone), pain during sexual intercourse (dyspareunia), a decrease in bone mass (osteoporosis), and hot flashes resembling those of menopause. Symptoms of males with Kallmann Syndrome may be an absence of testes (male reproductive gland), testes that have not descended into the scrotum (cryptorchidism), a small penis (micropenis) or an absence of external genitals (sex organs). A very rare form of Kallmann Syndrome includes partial or total paralysis of the muscles in the lower half of the body (spastic paraplegia). Causes People with Kallmann Syndrome experience abnormal development of the part of the brain concerned with the sense of smell (the rhinencephalon). This abnormal development interferes with the communication between part of the brain (the hypothalamus) and the gland at the base of the brain that secretes hormones into the blood (the pituitary). The result is an absence of the hormone that stimulates reproduction in men (LH or luteinize Hormone) and women (FSH or Follicle-stimulating hormone), which causes abnormal secondary sex characteristics and infertility. Kallmann Syndrome can be inherited as an autosomal dominant, autosomal recessive, or X-linked recessive disorder. The X-linked form is thought to be caused by a deletion on the short arm of the X chromosome at the location of the KALIG-1 gene. 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. X-linked recessive disorders are conditions which are coded on the X chromosome. Females have two X chromosomes, but males have one X chromosome and one Y chromosome. Therefore, in females, disease traits on the X chromosome can be masked by the normal gene on the other X chromosome. Since males only have one X chromosome, if they inherit a gene for a disease present on the X, it will be expressed. Men with X-linked disorders transmit the gene to all their daughters, who are carriers, but never to their sons. Women who are carriers of an X-linked disorder have a fifty percent risk of transmitting the carrier condition to their daughters, and a fifty percent risk of transmitting the disease to their sons. Affected Population Kallmann Syndrome affects males five times more often than females. The occurrence of this disorder is one in ten thousand males and one in every fifty thousand females. Related Disorders Symptoms of the following disorders can be similar to those of Kallmann Syndrome. Comparisons may be useful for a differential diagnosis: Klinefelter Syndrome is a rare disorder that effects males. It is characterized by the presence of one or more extra X-chromosomes in at least one tissue. Abnormally decreased functional activity of the sex glands (gonad) results in retardation of growth and sexual development. Other symptoms of Klinefelter Syndrome may be abnormally large mammary glands in the breasts, small testes, lack of sperm, and abnormally small penis. (For more information on this disorder choose "Klinefelter Syndrome" as your search term in the Rare Disease Database). Noonan Syndrome is a rare genetic disorder that can affect both males and females. This disorder is characterized by a lack of sexual development, short stature, possible mental retardation, a webbed neck, skeletal and/or heart defects, and deformity of the elbow. (For more information on this disorder choose "Noonan" as your search term in the Rare Disease Database). Turner Syndrome is a rare genetic disorder that affects females. This disorder is characterized by a lack of sexual development, small stature, possible mental retardation, a webbed neck, or heart defects. Individuals with this disorder have female characteristics, but they do not develop secondary sexual characteristics. (For more information on this disorder choose "Turner Syndrome" as your search term in the Rare Disease Database). Therapies: Standard Patients with Kallmann Syndrome may be successfully treated with luteinizing hormone-releasing hormone (LHRH) to stimulate secondary sex characteristics and sexual function. Fertility in both sexes may be obtained with gonadotropin-releasing hormone (GNRH) therapy and in some cases a combination of GNRH and spermatogenesis (used to induce the formation of sperm in males). The production of sex cells may be achieved with repeated injections of human clorionic gonadotropin (hCG) in males, and human menopausal gonadotropin (hMG) in females. Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive. Therapies: Investigational This disease entry is based upon medical information available through July 1992. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Kallmann Syndrome, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Forward Face 560 First Ave. New York, NY 10016 (212) 263-5205 (800) 422-FACE NIH/National Institute of Child Health and Human Development 9000 Rockville Pike Bethesda, MD 20892 301-496-5751 For genetic information and genetic counseling referrals: 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 MENDELIAN INHERITANCE IN MAN, 9th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1990. Pp. 546, 1283, 1660. INTERNAL MEDICINE, 2nd Ed.: Jay H. Stein, Editor-In-Chief; Little, Brown and Co., 1987. Pp. 1985-6. CECIL TEXTBOOK OF MEDICINE, 19th Ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Editors; W.B. Saunders Co., 1990. Pp. 1416-17. BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief; Blackwell Scientific Publications, 1990. Pp. 1000. PRINCIPLES OF NEUROLOGY, 4th Ed.; Raymond D. Adams, M.D. and Maurice Victor, M.D., Editors; McGraw-Hill Information Services Company, 1989. Pp. 185. OPHTHALMIC MIDLINE DYSGENESIS IN KALLMANN SYNDROME: M.J. Jaffe, et al.; Ophthalmic Paediatr Genet (November 1987, issue 8(3)). Pp. 171-4.