$Unique_ID{BRK03792} $Pretitle{} $Title{Growth Hormone Deficiency} $Subject{Growth Hormone Deficiency GHD Turner Syndrome Cystic Fibrosis Down Syndrome CHARGE association Laron Dwarfism} $Volume{} $Log{} Copyright (C) 1990 National Organization for Rare Disorders, Inc. 866: Growth Hormone Deficiency ** IMPORTANT ** It is possible that the main title of the article ( Growth Hormone Deficiency) is not the name you expected. Please check the SYNONYM listing to find the alternate names and disorder subdivisions covered by this article. Synonyms GHD Information on the following diseases can be found in the Related Disorders section of this report: Turner Syndrome Cystic Fibrosis Down Syndrome CHARGE association Laron Dwarfism 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. Growth Hormone is manufactured in the pituitary gland. If it is missing or reduced in quantity during infancy or childhood, it results in growth retardation, short stature and other maturation delays. Growth Hormone Deficiency (GHD) causes an absence or delay of lengthening and widening of the skeletal bones inappropriate to the chronological age of the child. A sufficient quantity of growth hormone is required during childhood to maintain growth and normalize sexual maturity. In some cases the onset of the disorder occurs prenatally (before birth), and in others the condition occurs months or years later. Laboratory testing is necessary before a diagnosis of Growth Hormone Deficiency is made because growth and maturity delays can be caused by a wide variety of other factors, including normal genetic influences. Symptoms Growth increments are the most important criteria in the diagnosis of Growth Hormone Deficiency. Normal levels of growth usually follow a pattern and if growth during a recorded six to twelve month period is within those levels it is unlikely that a growth disorder exists. Growth in the first six months of life is usually 16 to 17 cm. and in the second six months approximately 8 cm. During the second year 10 or more cm is normal. Growth in the third year should equal 8 cm or more and in the fourth year 7 cm. In the years between four and ten, an average of 5 or 6 cm is normal. Ten percent deviation in these norms is the standard in assessing a growth abnormality. If a child falls below the ten per cent deviation in growth he/she should then be tested for abnormally low levels of growth hormone. The child with GHD is usually of normal weight and length at birth. The infant may become hypoglycemic (low blood sugar) during the newborn period. If male, the child may have a small penis. Symptoms that children with GHD usually have in common are abnormal rates of development of facial bone, slow tooth eruption, delayed skeletal development, fine hair and poor nail growth. They may also experience obesity, a high pitched voice and delayed closure of the front bones of the skull (fontanels). Causes The Growth Hormone gene is located on the long arm of chromosome 17. This knowledge makes genetic testing and counseling possible. Growth Hormone Deficiency occurs in some children for no apparent reason. In others it may be inherited or run in families (familial). There are several types of GHD: Growth Hormone Deficiency IA is characterized by growth retardation before birth (prenatally). The child is small in relation to it's brothers and sisters. The infant usually has a normal response to administration of human growth hormone (hGH) at first, then develops antibodies to the hormone. This form of GHD results in very short adults. It is inherited as an autosomal-recessive trait. Growth Hormone Deficiency IB is similar to IA, however there is some growth hormone (GH) present in the child at birth. The child may respond to hGH treatments. It is inherited as an autosomal-recessive trait. Growth Hormone Deficiency IIB is similar to IB, however, it is inherited through an autosomal-dominant mode. Growth Hormone Deficiency III is similar to the above, however, it is inherited through X-linked transmission affecting only males. 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. In 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 Growth Hormone Deficiency affects males and females equally except for GHD III which affects only males. It is, however, associated very closely with other disorders such as: Down syndrome, CHARGE association, cystic fibrosis, chronic renal failure and Turner syndrome to name a few. There may be approximately 10,000 to 15,000 children in the United States with pituitary dwarfism caused by GHD. Related Disorders Symptoms of the following disorders can be similar to those of Growth Hormone Deficiency. Comparisons may be useful for a differential diagnosis: Turner Syndrome is a genetic disorder affecting females which is characterized by a lack of sexual development, small stature, possible mental retardation, a webbed neck, heart defects, and various other congenital abnormalities. Individuals have an XO karyotype; i.e.; they have neither the second X chromosome that characterizes females nor the Y chromosome of males. Despite the unusual genetic karyotype, people with Turner syndrome are females. (For more information on this disorder, choose "Turner" as your search term in the Rare Disease Database). Cystic Fibrosis is an inherited disorder that affects the exocrine, or outward-secreting glands of the body. It affects children and young adults. The main consequences are related to the mucus producing glands. The secreted mucus is thick and sticky, clogging and obstructing air passages in the lungs and pancreatic bile ducts. Cystic Fibrosis also causes dysfunction of salivary and sweat glands. There may also be decreased appetite, weight loss, failure to gain weight or grow normally, decreased exercise tolerance and enlarged and blue finger tips (digital clubbing). (For more information on this disorder, choose "Cystic Fibrosis" as your search term in the Rare Disease Database). Down Syndrome is the most common and readily identifiable genetic condition associated with mental retardation. It is caused by a chromosomal abnormality. One additional chromosome is present in each cell and this extra genetic material changes the orderly development of body and brain. There are over 50 clinical signs of Down syndrome, but it is rare to find all or even most of them in one person. Some common characteristics include: Poor muscle tone Slanting eyes with epicanthic folds Growth retardation with short adult height Transverse crease on the palm Short neck Small head Small mouth Flat nose bridge (For more information on this disorder, choose "Down" as your search term in the Rare Disease Database). CHARGE Association is a very rare disorder characterized by a variety of symptoms. At least four of the following six characteristics are necessary for the diagnosis of CHARGE Association: Coloboma of the iris, Heart Disease, Atresia of the choanae, Retarded growth and development and central nervous system abnormalities, underdevelopment of the Genitals, Ear abnormalities and loss of hearing. The first initials of Coloboma, Heart, Atresia, Retardation, Genitals and Ear, compose the word CHARGE. (For more information on this disorder, choose "CHARGE" as your search term in the Rare Disease Database). Laron Dwarfism is characterized by proportionate severe short stature which is evident at birth or soon after. Along with growth retardation there are delays in tooth eruption. There is also disproportion between the growth of the head and jaw, a saddle nose and deep set eyes. Sexual development is slow but it does occur. The usual age of sexual maturation in boys with Laron Dwarfism is about 22 years of age. In females with the disorder, sexual maturation usually takes place between 16 to 19 years of age. Hands and feet are smaller than normal. Obesity and a high-pitched voice may also be present. Laron Dwarfism is a disorder of growth hormone receptors. The body is unable to use the growth hormone that it produces. A high percentage of the patients have extremely low blood sugar levels (hypoglycemia). (For more information on this disorder, choose "Laron" as your search term in the Rare Disease Database). Therapies: Standard Testing is very important in determining if the child with growth retardation does indeed have Growth Hormone Deficiency. The child is tested using one of the following tests: the insulin-arginine-estrogen test, the GH-plasma-exercise, the clonidine or the L-dopa and propranolol tests. When a diagnosis of GHD is made, treatment can then be instituted. The question of whether short children whose levels of growth hormone have not been tested, should be treated with human growth hormone (hGH), is very controversial since commercially available biotechnology engineered human growth hormone (hGH) is very expensive and many health insurance companies will not reimburse for the product unless laboratory tests confirm GHD. Moreover, adverse effects of hGH on healthy short children who do not have a deficiency of the hormone have not been adequately assessed and long-term side effects are unknown. In the past, growth hormone recovered from human cadaver pituitaries was used. However, because of problems obtaining sufficient quantities and the possibility of transferring disease, that method is no longer used. Recombinant (biotechnology engineered) hGH is available on the U.S. market as Protropin (Genentech) and Humatrope (Eli Lilly), as an injection. Children with GHD are usually started on small doses of recombinant human growth hormone as soon as the disorder is recognized. The dosage is gradually increased to its highest during puberty, and discontinued by approximately age 17. Genetic counseling may be of benefit for patients with GHD and their families. Therapies: Investigational Studies continue on the causes and treatment of GHD and other growth related diseases. Scientists are especially investigating the physiology of growth hormone receptors which may lead to additional pharmaceutical interventions in the future. This disease entry is based upon medical information available through October 1991. 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 Growth Hormone Deficiency, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783-1783 203-746-6518 The Magic Foundation 1327 N. Harlem Ave. Oak Park, IL 60302 (708) 383-0808 Human Growth Foundation 7777 Leesburg Pike P.O. Box 3090 Falls Church, VA 22043 703-883-1773 800-451-6434 Short Stature Foundation 17200 Jamboree Rd., Suite J Irvine, CA 92714-5828 (714) 474-4554 800-24 DWARF Little People of America P.O. Box 633 San Bruno, CA 94066 415-589-0695 (a support group for adults with growth deficiencies) NIH/National Institute of child Health and Human Development (NICHD) 9000 Rockville Pike Bethesda, MD 20892 301-496-5133 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. 377-80, 887-8, 1426-27. CECIL TEXTBOOK OF MEDICINE, 19th Ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Editors; W.B. Saunders Co., 1990. Pp. 1290-7, 2205. SMITH'S RECOGNIZABLE PATTERNS OF HUMAN MALFORMATION, 4th Ed.: Kenneth L. Jones, M.D., Editor; W.B. Saunders Co., 1988. Pp. 614-8, 762-3. DIAGNOSTIC RECOGNITION OF GENETIC DISEASE, William L. Nyhan, et al.; Lea & Febiger, 1987. Pp. 706-9, 712, 718. CLINICAL PEDIATRIC ENDOCRINOLOGY, Solomon A. Kaplan,: W.B. Saunders Co., 1990. Pp. 1-56. GROWTH HORMONE THERAPY, Shulman, L, et al.; Am Fam Physician, May, 1990, (issue 41 (5)). Pp. 1541-6. BIOSYNTHETIC HUMAN GROWTH HORMONE IN THE TREATMENT OF GROWTH HORMONE DEFICIENCY., Holcombe, J.H. et al.; Acta Paediatr Scand Suppl, 1990, (issue 367). Pp. 44-8. URINARY GROWTH HORMONE EXCRETION AS A SCREENING TEST FOR GROWTH HORMONE DEFICIENCY, Walker, J.M, et al,; Arch Dis Child, January, 1990 (issue 65 (1)). Pp. 89-92. GROWTH HORMONE FOR SHORT STATURE NOT DUE TO CLASSIC GROWTH HORMONE DEFICIENCY., Cara, J.F., et al.; Pediatr Clin North Am., December, 1990, (issue 37 (6)). Pp. 1229-54.