Inherited Dwarfism

Dwarfism is characterized by having a full grown height of 4'10" or less. There are around 200 known medical conditions that cause dwarfism, most of which involve genetic mutations that interfer with normal growth. Most people with dwarfism have a normal lifespan and normal intelligence level, obtaining careers as lawyers, doctors, ministers, artisans, teachers, and more. Two of the most common types of dwarfism are pituitary dwarfism and achondroplasia.

Pituitary Dwarfism

    Pituitary dwarfism, or hypopituitary dwarfism, is caused by a growth hormone deficiency. This type of dwarfism is characterized by having a short stature, but overall proportional body. These people are sometimes called midgets, but because of the negative connotation of the word it is becoming used less often.

    Normally the hypothalamus of the brain sends chemical messengers to the pituitary gland to produce growth hormone in the front part of the pituitary. In pituitary dwarfism there is a mutation in one of the enzymes along this pathway, leading to a deficient amount of growth hormone release. For example, a person may inherit defective genes that cause the production of defective receptors for growth hormone releasing hormone (GHRHR), therefore there is no signal produced to stimulate growth. Other causes of pituitary dwarfism include physical damage of the hypothalamus or pituitary gland. People at risk are newborns that endured trauma or lack of oxygen during the perinatal period (labor, delivery, and the first few days as a newborn). If the hypothalamus is damaged in this way, no messenger is sent to the pituitary gland to produce growth hormone.

    Symptoms of abnormal growth usually are not seen until the child is two or three years old because this is when a dramatic increase in growth hormone is needed for normal growth. Another symptom besides short stature and growth hormone deficiency is low blood sugar. This is because growth hormone usually opposes the action of insulin, so without it insulin is able sequester a larger amount of glucose than normal from the blood into tissue.

    Diagnosis of pituitary dwarfism includes measuring the level of growth hormone in the blood. Levels of growth hormone are difficult to accurately measure because its blood concentration is usually low during the day and highest during deep sleep. Growth hormone release may be stimulated by clonidine or Ldopa before it is measured.

    Treatment consists of injections of human growth hormone beginning when the child is young. Growth hormones of animals do not work, and therefore cannot be used. In order to have large quantities of human growth hormone, it is artificially produced by recombination techniques. Treatment by growth hormone replacement has proved to be very successful in most patients. Most are able to obtain normal height by adulthood. A side effect of the injections is the worsening of diabetes.

Achondroplasia

    People with achondroplasia are characterized by short stature, abnormal bone growth, disproportionately short arms and legs, large head, and characteristic facial features. Achondroplasia is a skeletal dysplasia caused by a mutation of the FGFR3 gene (fibroblast growth factor receptor 3). It is an autosomal dominant allele, usually resulting from a new gene mutation from parent to child. 80% of these dwarfs have two parents of normal height.

    98% of achondroplasia cases are a result of a Gly380Arg mutation (most likely a G to A point mutation at nucleotide 1138) in the FGFR3 gene. FGFR3 negatively regulates bone growth, so that when it is activated it inhibits bone growth. The Gly380Arg mutation causes constitutive acivation of FGFR3, inhibiting further bone growth. This is called a gain of function mutation because it enhances the ability of the receptor.

    Growth hormone blood levels in children with achondroplasia are normal because it is not an abnormal release of growth hormone that is the problem. Studies involving the effects of growth hormone treatment on this type of dwarfism are currently being carried out. Growth hormone treatment seems to be helping, although it is necessary to wait for the current people in the studies to reach adulthood.

For images of dwarfs, check out our image page.
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