Risk Factors (Genetics & Inherited Conditions)
Etiology and Genetics (Genetics & Inherited Conditions)
Achondroplasia is inherited as an autosomal dominant disorder, meaning that a single copy of the mutation is sufficient to cause full expression of the syndrome. An affected individual has a 50 percent chance of transmitting the mutation to each of his or her children. Most cases of achondroplasia, however, result from spontaneous new mutation, so in these instances affected individuals will have unaffected parents. Advanced paternal age has been identified as a contributing factor in many spontaneous cases, and researchers using mouse models are endeavoring to identify aspects of deoxyribonucleic acid (DNA) replication or repair during spermatogenesis that could result in a predisposition to this mutation.
Homozygous achondroplasia, in which both copies of the gene carry the mutation, is a severe disorder that is invariably fatal either before or shortly after birth. Rare reports of marriages in which both partners have achondroplasia confirm the prediction that in such families 50 percent of the children will have achondroplasia, 25 percent will be unaffected, and 25 percent will die from the severe homozygous form of the condition.
Either of two mutations at nucleotide 1138 of the FGFR3 gene, found on the short arm of chromosome 4 at position 4p16.3, will result in achondroplasia. The normal product of this gene, fibroblast growth factor receptor 3, is a protein that exerts negative regulatory control...
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Symptoms (Genetics & Inherited Conditions)
Patients with achondroplasia have short stature, a long trunk, and shortened limbs, which are noticeable at birth. Adults usually reach a height of between 42 and 56 inches. An individual’s head is large and his or her forehead is prominent, and portions of the face can be underdeveloped. At birth, the legs appear straight, but as a child begins to walk, he or she develops a knock-knee or bowed-leg deformity. The hands and the feet appear large, but the fingers and toes are short and stubby; straightening of the arm at the elbow may be restricted but usually does not keep a patient with achondroplasia from doing any specific activities. Children may develop an excessive curve of the lower back and a waddling walking pattern.
Other common symptoms include weight control problems; bowed legs; middle ear infections, especially in children, which, if not treated properly, can result in hearing loss; dental problems (from overcrowding of teeth); hydrocephalus (water on the brain); and neurologic and respiratory problems. Individuals also experience fatigue, pain, and numbness in the lower back and spine. Spinal compression may occur in the upper back or where the spinal cord exits from the skull in the back of the neck; compression at this latter site may cause sleep apnea or even death if not recognized and treated early. A magnetic resonance imaging (MRI) or a computed tomography (CT) scan evaluation can help detect these...
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Screening and Diagnosis (Genetics & Inherited Conditions)
The diagnosis for achondroplasia includes clinical evaluation and radiographs. Molecular genetic testing can be used to detect a mutation in the FGFR3 gene; such testing is 99 percent sensitive and is performed in clinical laboratories. A doctor can usually diagnose the disorder in a newborn by observing physical symptoms. To confirm that dwarfism is caused by achondroplasia, X rays are taken.
It is important that patients follow their doctors’ advice to make sure that spinal stenosis does not develop. The physician can evaluate the strength of a patient’s extremities and bladder control. Weakness and loss of bladder control are both signs of developing spinal stenosis.
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Treatment and Therapy (Genetics & Inherited Conditions)
Unfortunately there is currently no treatment that can cure this condition. Because it is now known that achondroplasia is caused by an absence of growth factor receptor, scientists are exploring ways to create alternate growth factors that can bypass the missing receptor and lead to normal bone growth. Such treatments are still well in the future but may offer the possibility of enhanced stature to future families who have children with achondroplasia.
Treatment with human growth hormone has been used for more than a decade and effectively increases bone growth rate, at least in the first year of life. There have been few studies looking at whether children treated with growth hormone achieve greater (or normal) adult heights.
Surgery is sometimes needed to correct specific skeletal deformities. Spinal fusion is a surgery to permanently connect otherwise separate vertebrae. This surgery is performed for patients with significant spinal kyphosis.
Laminectomy is a surgical procedure to open the spinal canal to relieve pressure on the compressed spinal cord from spinal stenosis. Spinal stenosis, a narrowing of the spinal canal, is the most serious complication of achondroplasia.
In an osteotomy, the bones of the leg are cut and allowed to heal in the correct anatomical position. This procedure is used for patients with severe knock-knees or bowed legs.
While osteotomy has primarily been used to...
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Prevention and Outcomes (Genetics & Inherited Conditions)
Because achondroplasia is an inherited disorder, there are no preventive measures. The prognosis depends on the severity of the condition. Patients who have two copies of the deficient gene (one from each parent, also known as homozygous) generally die a few weeks to months after birth. Those with one copy (from only one parent, also known as heterozygous) have a normal life span and intelligence, although children often take longer to develop normal motor skills and there is an increased risk of death in the first year of life due to respiratory problems. Patients are usually independent in their daily life activities. Many of these patients, in fact, have gone on to do great things in life.
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Further Reading (Genetics & Inherited Conditions)
Aldegheri, R., and C. Dall’Oca. “Limb Lengthening in Short Stature Patients.” Journal of Pediatric Orthopaedics, Part B 10, no. 3 (July, 2001): 238-247.
Aviezer D., M. Golembo, and A. Yayon. “Fibroblast Growth Factor Receptor-3 as a Therapeutic Target for Achondroplasia—Genetic Short Limbed Dwarfism.” Current Drug Targets 4, no. 5 (July, 2003): 353-365.
Beers, Mark H., ed. The Merck Manual of Medical Information. 2d home ed., new and rev. Whitehouse Station, N.J.: Merck Research Laboratories, 2003.
Boulet, S., et al. “Prenatal Diagnosis of Achondroplasia: New Specific Signs.” Prenatal Diagnosis 29, no. 7 (July, 2009): 697-702.
EBSCO Publishing. Health Library: Achondroplasia. Ipswich, Mass.: Author, 2009. Available through http://www.ebscohost.com.
Kumar, Vinay, Abul K. Abbas, and Nelson Fausto, eds. Robbins and Cotran Pathologic Basis of Disease. 7th ed. St. Louis: MD Consult, 2004.
Parens, Erik, ed. Surgically Shaping Children: Technology, Ethics, and the Pursuit of Normality. Baltimore: Johns Hopkins University Press, 2006.
Pauli, Richard M. “Achondroplasia.” In Management of Genetic Syndromes, edited by Suzanne B. Cassidy and Judith E. Allanson. 2d ed. Hoboken, N.J.: Wiley-Liss, 2005.
Shirley, E. D., and M. C. Ain. “Achondroplasia: Manifestations and Treatment.” Journal of...
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Web Sites of Interest (Genetics & Inherited Conditions)
American Academy of Pediatrics. http://www.aap.org
Genetics Home Reference. http://ghr.nlm.nih.gov
Little People of America. http://www.lpaonline.org
Little People of Ontario. http://www.lpo.on.ca
March of Dimes. http://www.modimes.org
United States National Library of Medicine. http://www.nlm.nih.gov
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Achondroplasia (Encyclopedia of Genetic Disorders)
Achondroplasia is a common form of dwarfism or short stature due to an autosomal dominant mutation (a mutation on one of the first 22 "non-sex" chromosomes) that causes an individual to have short stature with disproportionately short arms and legs, a large head, and distinctive facial features, including a prominent forehead and a flattened midface.
Achondroplasia is a genetic form of dwarfism due to a problem of bone growth and development. There are many causes for dwarfism, including hormone imbalances and metabolic problems. Achondroplasia belongs to a class of dwarfism referred to as a chrondrodystrophy or skeletal dysplasia. All skeletal dysplasias are the result of a problem with bone formation or growth. There are over 100 different types of skeletal dysplasia. Achondroplasia is the most common and accounts for half of all known skeletal dysplasias.
Achondroplasia is easily recognizable. Affected individuals have disproportionate short stature, large heads with characteristic facial features, and disproportionate shortening of their limbs. Most individuals with achondroplasia have a normal IQ. The motor development of infants is delayed due to hypotonia (low muscle tone) and their physical...
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Achondroplasia (Encyclopedia of Medicine)
Achondroplasia is the most common cause of dwarfism, or significantly abnormal short stature.
Achondroplasia is one of a number of chondodystrophies, in which the development of cartilage, and therefore, bone is disturbed. The disorder appears in approximately one in every 10,000 births. Achondroplasia is usually diagnosed at birth, owing to the characteristic appearance of the newborn.
Normal bone growth depends on the production of cartilage (a fibrous connective tissue). Over time, calcium is deposited within the cartilage, causing it to harden and become bone. In achondroplasia, abnormalities of this process prevent the bones (especially those in the limbs) from growing as long as they normally should, at the same time allowing the bones to become abnormally thickened. The bones in the trunk of the body and the skull are mostly not affected, although the opening from the skull through which the spinal cord passes (foramen magnum) is often narrower than normal, and the opening (spinal canal)...
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