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 differences (large heads and small bones). The motor development of children with achondroplasia eventually catches up with that of their peers. Individuals with achondroplasia can have medical complications that range from mild to severe. Because of the differences in their bone structure, these individuals are prone to middle ear infections. They are also at risk for neurologic problems due to spinal cord compression. The spinal canal (which holds the spinal cord) is smaller than normal in achondroplasia. The American Academy of Pediatrics' Committee on Genetics has developed guidelines for the medical management of children with achondroplasia.
The short stature of achondroplasia can be a socially isolating and physically challenging. Most public places are not adapted to individuals of short stature and this can limit their activities. Children and adults with achondroplasia can be socially ostracized due to their physical appearance. Many people erroneously assume that individuals with achondroplasia have limited abilities. It is very important to increase awareness with educational programs and to take proactive steps to foster self-esteem in children with achondroplasia.
Genes contain the instructions that tell a body how to form. They are composed of four different chemical bases–adenine (A), thymine (T), cytosine (C), and guanine (G). These bases are arranged like words in a sentence and the specific order of these four bases provide the instructions that a cell needs to form a protein.
FGFR (fibroblast growth factor receptor) genes provide the instruction for the formation of a cell receptor. Every cell in the body has an outer layer called a cell membrane that serves as a filter. Substances are transported into and out of the cells by receptors located on the surface of the cell membrane. Every cell has hundreds of different types of receptors. The fibroblast growth factor receptor transports fibroblast growth factors into a cell. Fibroblast growth factors play a role in the normal growth and development of bones. When the receptors for fibroblast growth factors do not work properly, the cell does not receive enough fibroblast growth factors and results in abnormal growth and development of bones.
Achondroplasia is caused by mutations in the FGFR3 gene. Two specific mutations account for approximately 99% of achondroplasia. The FGFR gene is comprised of 2,520 bases. In a normal (non-mutated) gene, base number 1138 is guanine (G). In most individuals with achondroplasia (98%), this guanine (G) has been replaced with adenine (A). In a small number of individuals with achondroplasia (1%), this guanine (G) has been replaced with cytosine (C). Both of these small substitutions cause a change in the fibroblast growth factor receptor (FGFR) that affects the function of this receptor.
Mutations in the FGFR3 gene are inherited in an autosomal dominant manner. Every individual has two FGFR3 genes—one from their father and one from their mother. In an autosomal dominant disorder, only one gene has to have a mutation for the person to have the disorder. Over 80% of individuals with achondroplasia are born to parents with average stature. Their achondroplasia is the result of a de novo or new mutation. No one knows the cause of de novo mutations or why they occur so frequently in achondroplasia. For reasons that are not yet understood, most new mutations occur in the FGFR3 gene that is inherited from the average-size father.
An individual with achondroplasia has a 50% chance of passing on their changed (mutated) gene to their children. An achondroplastic couple (both parents have achondroplasia) has a 25% chance that they will have a
Because individuals with other forms of dwarfism are often misdiagnosed with achondroplasia, the exact incidence of achondroplasia is unknown. Estimates of the incidence of achondroplasia vary between 1/10,000 to 1/40,000 births. It is estimated that there are approximately 15,000 individuals with achondroplasia in the United States and 65,000 worldwide. Achondroplasia affects males and females in equal numbers.
Signs and symptoms
Individuals with achondroplasia have disproportionate short stature, large heads with characteristic facial features, and rhizomelic shortening of their limbs. Rhizomelic means "root limb." Rhizomelic shortening of the limbs means that those segments of a limb closest to the body (the root of the limb) are more severely affected. In individuals with achondroplasia, the upper arms are shorter than the forearms and the upper leg (thigh) is shorter than the lower leg.
In addition to shortened limbs, individuals with achondroplasia have other characteristic limb differences. People with achondroplasia have a limited ability to rotate and extend their elbows. They generally develop bowed legs and may have in-turned toes. Their hands and feet are short and broad, as are their fingers and toes. Their hands have been described as having a "trident" configuration. This term is based upon the trident fork used in Greek mythology and describes the unusual separation of their middle fingers. This unusual separation gives their hands a "three-pronged" appearance with the thumb and two small fingers on the side and the index and middle finger in the middle.
Individuals with achondroplasia have similar facial features and a large head (megalencephaly) due to the difference in the growth of the bones of the face and head. The exact reason for the increase in head size is not known, but it reflects increased brain size and can sometimes be due to hydrocephalus. People with achondroplasia have a protruding forehead (frontal bossing) and a relatively prominent chin. The prominent appearance of the chin is in part due to the relative flatness of their midface. While people with achondroplasia do resemble one another, they also resemble their family of origin.
Individuals with achondroplasia have shortening of their long bones. Women with achondroplasia have an average adult height of 48 in (122 cm). Men have an average adult height of 52 in (132 cm).
Achondroplasia is generally diagnosed by physical examination at birth. The characteristic findings of short stature, rhizomelic shortening of the limbs, and specific facial features become more pronounced over time. In addition to being diagnosed by physical examination, individuals with achondroplasia have some specific bone changes that can be seen on an x ray. These include a smaller spinal canal and a small foramen magnum. The foramen magnum is the opening at the base of the skull. The spinal cord runs from the spinal canal through the foramen magnum and connects with the brain.
The diagnosis of achondroplasia can also be made prenatally either by ultrasound (sonogram) or by prenatal DNA testing. Sonograms use sound waves to provide an image of a fetus. The physical findings of achondroplasia (shortened long bones, trident hand) can be detected in the third trimester (last three months) of a pregnancy. Prior to the last three months of pregnancy, it is difficult to use a sonogram to diagnose achondroplasia because the physical features may not be obvious. Because of the large number of skeletal dysplasias, it can be very difficult to definitively diagnose achondroplasia by sonogram. Many other dwarfing syndromes can look very similar to achondroplasia on a sonogram.
Prenatal testing can also be done using DNA technology. A sample of tissue from a fetus is obtained by either chorionic villi sampling (CVS) or by amniocentesis. Chorionic villi sampling is generally done between 10-12 weeks of pregnancy and amniocentesis is done between 16-18 weeks of pregnancy. Chorionic villi sampling
Prenatal DNA testing for achondroplasia is not routinely performed in low-risk pregnancies. This type of testing is generally limited to high-risk pregnancies, such as those in which both parents have achondroplasia. It is particularly helpful in determining if a fetus has received two abnormal genes (homozygous achondroplasia). This occurs when both parents have achondroplasia and each of them passes on their affected gene. The baby gets two copies of the achondroplasia gene. Babies with homozygous achondroplasia are much more severely affected than babies with heterozygous achondroplasia. Infants with homozygous achondroplasia generally die shortly after birth due to breathing problems caused by an extremely small chest.
DNA testing can also be performed on blood samples from children or adults. This is usually done if there is some doubt about the diagnosis of achondroplasia or in atypical cases.
Treatment and management
There is no cure for achondroplasia. The recommendations for the medical management of individuals with achondroplasia have been outlined by the American Academy of Pediatrics' Committee on Genetics. The potential medical complications of achondroplasia range from mild (ear infections) to severe (spinal cord compression). By being aware of the potential medical complications and catching problems early, it may be possible to avert some of the long-term consequences of these complications. An individual with achondroplasia may have some, all, or none of these complications.
All children with achondroplasia should have their height, weight, and head circumference measured and plotted on growth curves specifically developed for children with achondroplasia. Measurements of head circumference are important to monitor for the development of hydrocephalus—a known but rare (<5%) complication of achondroplasia. Hydrocephalus (or water on the brain) is caused by an enlargement of the fluid-filled cavities of the brain (ventricles) due to a blockage that impedes the movement of the cerebrospinal fluid. Suspected hydrocephalus can be confirmed using imaging techniques such as a CT or MRI scan and can be treated with neurosurgery or shunting (draining) if it causes severe symptoms. Any child displaying neurologic problems such as lethargy, abnormal reflexes, or loss of muscle control should be seen by a neurologist to make sure they are not experiencing compression of their spinal cord. Compression of the spinal cord is common in individuals with achondroplasia because of the abnormal shape and small size of their foramen magnum (opening at the top of the spinal cord).
All children with achondroplasia should be monitored for sleep apnea, which occurs when an individual stops breathing during sleep. This can occur for several reasons, including obstruction of the throat by the tonsils and adenoids, spinal cord compression, and obesity. Individuals with achondroplasia are more prone to sleep apnea due to the changes in their spinal canal, foramen magnum, and because of their short necks. Treatment for sleep apnea depends on its cause. Obstructive sleep apnea is treated by surgically removing the tonsils and adenoids. Neurosurgery may be required to treat sleep apnea
Other potential problems in children with achondroplasia include overcrowding of the teeth (dental malocclusion), speech problems (articulation), and frequent ear infections (otitis media). Dental malocclusion (overcrowding of teeth) is treated with orthodontics. All children with achondroplasia should be evaluated by a speech therapist by two years of age because of possible problems with the development of clear speech (articulation). Articulation problems may be caused by orthodontic problems. Due to the abnormal shape of the eustachian tube in an individual with achondroplasia, they are very prone to ear infections (otitis media). Approximately 80% of infants with achondroplasia have an ear infection in the first year of life. About 78% of these infants require ventilation tubes to decrease the frequency of ear infections.
Weight management is extremely important for an individual with achondroplasia. Excess weight can exacerbate many of the potential orthopedic problems in an individual with achondroplasia such as bowed legs, curvature of the spine, and joint and lower back pain. Excess weight can also contribute to sleep apnea. Development of good eating habits and appropriate exercise programs should be encouraged in individuals with achondroplasia. These individuals should discuss their exercise programs with their health care provider. Because of the potential for spinal cord compression, care should be used in choosing appropriate forms of exercise.
The social adaptation of children with achondroplasia and their families should be closely monitored. Children with visible physical differences can have difficulties in school and socially. Support groups such as Little People of America can be a source of guidance on how to deal with these issues. It is important that children with achondroplasia not be limited in activities that pose no danger. In addition to monitoring their social adaptation, every effort should be made to physically adapt their surroundings for convenience and to improve independence. Physical adaptations can include stools to increase accessibility and lowering of switches and counters.
Two treatments have been used to try to increase the final adult height of individuals with achondroplasia–limb-lengthening and growth hormone therapy. There are risks and benefits to both treatments and as of 2001, they are still considered experimental.
Limb-lengthening involves surgically attaching external rods to the long bones in the arms and legs. These rods run parallel to the bone on the outside of the body. Over a period of 18-24 months, the tension on these rods is increased, which results in the lengthening of the underlying bone. This procedure is long, costly, and has potential complications such as pain, infections, and nerve problems. Limb-lengthening can increase overall height by 12-14 in (30.5-35.6 cm). It does not change the other physical manifestations of achondroplasia such as the appearance of the hands and face. This is an elective surgery and individuals must decide for themselves
Growth hormone therapy has been used to treat some children with achondroplasia. Originally there was doubt about the effectiveness of this treatment because children with achondroplasia are not growth hormone deficient. However, studies have shown that rate of growth in children with achondroplasia treated with growth hormone does increase during the first two years of treatment. It is too early to say how effective this treatment is because the children involved in this study are still growing and have not reached their final adult height.
The prognosis for most people with achondroplasia is very good. In general, they have minimal medical problems, normal IQ, and most achieve success and have a long life regardless of their stature. The most serious medical barriers to an excellent prognosis are the neurologic complications that can arise in achondroplasia. Spinal cord compression is thought to increase the risk for SIDS to 7.5% in infants with achondroplasia and can lead to life-long complications such as paralysis if untreated. Obesity can increase the risk for heart disease and some studies have revealed an increased risk of unexplained death in the fourth and fifth decade of life.
Successful social adaptation plays an important role in the ultimate success and happiness of an individual with achondroplasia. It is very important that the career and life choices of an individual with achondroplasia not be limited by preconceived ideas about their abilities.
Ablon, Joan. Living with Difference: Families with Dwarf Children. Westport, CT: Praeger Publishing, 1988.
American Academy of Pediatrics Committee on Genetics. "Health Supervision for Children With Achondroplasia." Pediatrics 95, no 3 (March 1995): 443-51.
Little People of America, Inc. National Headquarters, PO Box 745, Lubbock, TX 79408. (806) 737-8186 or (888) LPA-2001. firstname.lastname@example.org. <http://www.lpaonline.org>.
The Human Growth Foundation. <http://www.hgfound.org/>
Little People of America: An Organization for People of Short Stature. <http://www.lpaonline.org/lpa.html>
Kathleen Fergus, MS