Genetics Northern California

Achondroplasia

Achondroplasia is the most common skeletal dysplasia. It happens about in 1/15,000 to 1/28,000 births. Individuals with achondroplasia have disproportionate short stature with the limbs being significantly shortened in relation to the length of the trunk (body). Life expectancy is normal for achondroplasia, however in a small percentage of individuals there is an increased risk for sudden death due to complications arising in infancy and early childhood. With appropriate medical care and management this risk is significantly decreased. Physical characteristics commonly seen in achondroplasia include: short stature due to short limbs, macrocephaly (large head), prominent forehead, depressed nasal bridge, trident configuration of fingers (split between 3rd and 4th fingers) and modestly constricted chest. Final adult height ranges from 43-53 inches (110-135 cm) in women and 45-57 inches (115-145 cm) for men.

Cause
Achondroplasia is caused by mutations in the gene for fibroblast growth factor receptor 3 (FGFR3). FGFR3 is a receptor that inhibits growth as part of a feedback loop that controls growth. The mutations causing achondroplasia "turn on" this receptor causing growth to be inhibited more than it would normally be. This inhibition leads to disproportionate growth of cartilaginous bone resulting in short limbs and other areas of decreased bone growth (e.g., midface). In achondroplasia, 98% of individuals have the exact same mutation into FGFR3 gene. The other 2% have similar mutations in FGFR3. Other mutations in FGFR3 produce conditions that are similar, but either milder or more severe than achondroplasia.

Achondroplasia is an autosomal dominant condition. Eighty percent (80%) of children with achondroplasia are born to parents who are both of average-stature (do not have achondroplasia). The achondroplasia in these children occurs as a sporadic (new) mutation in the embryo. Their parents are at very low risk of having another child with achondroplasia (0.02%). However, the individual with achondroplasia will have a 50% chance of passing their gene for achondroplasia to each of their children.

Achondroplasia is fairly similar in how it affects the individuals that have it. However, some people may have significantly more medical issues and disability related to their condition than others. There is no way to predict if a child will have mild or severe medical issues.

Diagnosis
Achondroplasia is diagnosed by clinical features (physical characteristics) and radiologic (x-ray) findings:

  • small skull base and small foramen magnum (an opening at the base of the skull)

  • narrowing of interpediculate distance in lumbar spine, short vertebral bodies (bones that make up the spine)

  • square iliac wings (hipbones)

  • flat acetabulae (the socket that connects the hip with the upper leg)

  • short thick long bones

  • flared metaphyses (the growing portion of a bone)

  • short first and middle fingers.

Genetic (DNA mutation) testing may be done to confirm the diagnosis or distinguish it from a similar condition. The diagnosis of achondroplasia is most often made during the newborn period. It may be detected by ultrasound in the 3rd trimester of a pregnancy.

Treatment/Services
The American Academy of Pediatrics has created Health Supervision Guidelines for achondroplasia that can be used as a general outline for care, management, anticipatory observation, and precautions. Growth curves for height and head circumference are available along with these guidelines.

1. Neurology
For the first few years, a child with achondroplasia should be monitored closely for neurological signs/symptoms of foramen magnum stenosis (narrowing or constriction). Risk factors include rapidly increased head circumference, clonus, brisk reflexes, sleep apnea, respiratory issues, and gastrointestinal reflux (heartburn) or aspiration (choking). Baseline monitoring includes: CT scan of brain and craniovertebral junction, sleep study, pediatric neurology evaluation every 6 months, and monthly head circumference measurement by pediatrician. In the most serious cases, surgical foramen magnum decompression may be needed.

2. Ear, Nose and Throat
There are multiple other potential medical issues that a child with achondroplasia should be monitored for. These children often have chronic otitis media (ear infections). Children should be followed carefully by Head and Neck Surgery (aka HNS, Ear Nose and Throat, or ENT). Bilateral myringotomy (ear tubes in both ears) is often performed and repeated multiple times in these children. The chronic otitis media may produce a short term hearing loss during the ages crucial for speech development. Baseline audiology evaluation in the first year plus subsequent annual evaluation is recommended to monitor for hearing loss. Preferential classroom seating, FM system for school and/or hearing aids may be considered if loss is persistent. Speech therapy may be required.

3. Sleep Apnea
Obstructive sleep apnea is also common in achondroplasia. The under development of the midface, large tonsils and adenoids, and redundant pharyngeal tissue (extra skin in the throat) can all contribute to sleep apnea. Removal of the tonsils and adenoids is common. If sleep apnea continues, B-PAP or C-PAP (Positive Airway Pressure) oxygen may be prescribed.

4. Orthodontia
Children with achondroplasia almost always require a orthodontia due to the midface hypoplasia and over growth of the mandible (lower jaw) which often results in malocclusion (incorrect positioning/rotation of the teeth), crowding, and cross bite. Usually general orthodontia can remedy these problems but in the most severe cases midface advancement may be considered.

5. Orthopedics
Kyphosis: From an orthopedic standpoint many children have some degree of flexible kyphosis (when the curve in the back causes the child to bend forward) before they begin to walk. In most cases, the kyphosis corrects itself when a child begins walking, however a minority of children require bracing and/or surgical fusion of the vertebrae to correct this curve.

Radial head subluxation: A majority of individuals with achondroplasia are unable to fully extend their arms at the elbow. In those with more significant limitation, radial head subluxation or dislocation is often seen. These dislocations should not be reduced (fixed)!

Leg bowing: Most children have some degree of leg bowing (genu varum). The most severe cases need to be treated surgically.

6. Motor Development
Motor development is often delayed due to the disproportion of the short limbs, flexibility of the ligaments (the cord-like tissues that connect bones to each other), and macrocephaly (large head). It is important not to push activities such as independent sitting as the child may have not yet developed the head control and trunk strength. Instead of sitting up, these children end up in a slumped position worsening the pressure on their spinal cord. Physical therapy may help if the child is significantly delayed. There are developmental milestone guidelines for achondroplasia that should be used to evaluate progress. Occupational therapy may be needed to help the child with fine motor skills such as holding a pen/pencil and using scissors. These activities can be difficult due to the small size of the hands and looseness of the joints.

7. Spinal Stenosis
All of the above issues have usually resolved or been treated by the teenage years. As a teenager or in adulthood a person may begin to develop lumbar lordosis (increasing inward curve of the lower back). In some cases this can lead to symptoms of spinal stenosis (narrowing of the spinal canal causing pressure to the spinal cord). The symptoms often occur after walking a distance or putting increased pressure on the lower spine such as jumping or falling. Symptoms include: numbness, weakness, and/or tingling into the hips and legs, pain/discomfort in the buttocks, hips, and legs. Most symptoms improve with rest and can often be prevented by exercises that strengthen the abdominal and back muscles (especially those connected to the spine). When symptoms increase to the point that the person cannot walk more than 1-2 blocks, begins to lose bowel or bladder control, or has constant symptoms, a lumbar laminectomy (surgery to release pressure on the spinal cord) may be recommended. An MRI along with clinical symptoms are used to evaluate the severity of spinal stenosis.

8. Weight Management
Weight management is a difficult issue for many people with achondroplasia, especially in adulthood. It is recommended that children be taught good eating habits and be served portions appropriate for their height rather than their age. Non-weight-bearing exercise, such as swimming and bicycling, is also strongly recommended and can help significantly with weight management.

9. Growth Hormone Therapy (GHT) and Extensive Limb Lengthening (ELL)
Growth hormone therapy and extensive limb lengthening have been used as a "treatment" for the short stature in achondroplasia. Research has yet to show that growth hormone therapy has any effect on final height in achondroplasia. Extensive limb lengthening can add about 1 foot of length to the limbs of an individual with achondroplasia. It is an arduous process that involves breaking the bone, placing a fixator device on that part of the limb and cranking the device every day so as to pull the bone apart as it is trying to heal. The process takes multiple years to lengthen the legs and upper arms and there are almost always has complications. It has not been shown to correct any of the other medical issues related achondroplasia. It is a controversial treatment as most people with achondroplasia do not feel that they need this treatment to be happy or successful in life. Kaiser does not provide either of these services, as they have not been shown to have medical benefit to those with achondroplasia.

10. Social Issues
Some of the most difficult aspects of having achondroplasia are not the medical issues, but rather the environmental and social issues that arise for a person of short stature and/or with an orthopedic disability. It is important to work with the family on their adjustment to the diagnosis and what that will mean for the child and their family. Individuals with achondroplasia and their families should receive assistance in developing strategies for functioning in a world made for taller people. Participation in household, school, and social activities are examples of activities that may all be significantly impacted by the condition. Stools, extenders for reaching, and extra time to get to class, are all examples of modifications that may be required. In addition to the functional aspects, being short-statured and orthopedically handicapped carries great stigma. It is important to help the people with achondroplasia and their families to mentally and emotionally prepare themselves for the teasing, staring, and ignorance they may face and to learn coping mechanisms and reactions to these behaviors. Little People of America (LPA) is the support organization for all people of short stature and their families. This organization can be extremely helpful in assisting with social adjustment and, more than anything else, letting people with short stature know that they are not alone in their circumstances.

Prenatal Diagnosis
First and early 2nd trimester prenatal diagnosis is available for couples in which one or both have achondroplasia and for average-statured parents who have had a previous child with achondroplasia. Chorionic villi sampling (CVS) or amniocentesis can be done for FGFR3 DNA mutation analysis. Ideally the mutations in the affected parents are identified prior to the prenatal testing. Parents who both have achondroplasia are at risk for having a baby with homozygous or double dominant achondroplasia which is a lethal condition.

Achondroplasia can be identified in utero by ultrasound. Couples at risk for homozygous achondroplasia and who choose not to have invasive prenatal diagnosis may have their pregnancy followed by ultrasound. Achondroplasia can also be detected in the pregnancy of an average-statured couple during the 3rd trimester if the mother happens to have an ultrasound for another indication. If short limbs are detected an amniocentesis may be offered to rule out a lethal form of skeletal dysplasia.


Created by: Ericka Okenfuss, MS, Deirdre Popplewell, RN
Reviewed by: Kimberly Barr, MS
Last Updated: Friday, March 9th, 2007 5:07 PM

Last reviewed: Tuesday, December 9th, 2008 11:03 AM