What is Achondroplasia?

Achondroplasia
Community College of Vermont
Anatomy and Physiology I (BIO-2011-VR01)
Spring 2013
By: Carrie A. Thibault

Achondroplasia, meaning “without cartilage formation” is the medical term given to the most common form of dwarfism in the world. An estimated 1 in 15,000 to 1 in 40,000 births are to infants with achondroplasia. The mutation of the fibroblast growth factor receptor 3 gene (FGFR3) in chromosome 4 was first discovered in 1994 by Dr. John Wasmut of the University of California, Irvine while looking for the genetic link to Huntington’s disease. Although it was not connected to Huntington’s disease, the connection to achondroplasia was undeniable. (Associated Press, 1994) Endochondral ossification is the process by which the cartilage turns into trabecular bone.. In achondroplasia, the mutation of the FGFR3 gene causes an arrest in the long bone growth by stopping the transition of cartilage to bone and causing abnormal cartilage growth. Diagnosis of achondroplasia can be done through genetic testing and radiography. X- rays, ultrasounds and Magnetic Resonance Imaging (MRI) can help determine diagnosis.. Diagnosis can also be done by observing physical characteristics and symptoms that are classically seen in patients with achondroplasia. Rapid diagnosis and symptomatic care of the patient with achondroplasia is the primary focus throughout the lifespan as there is no cure for the disease at this time.

Some of the symptoms of achondroplasia are typical and may indicate the disease early on such as a long narrow trunk, trident hand and hypoplasia of the mid-face. Achondroplasia in infants may be also suspected by a “larger than normal head size and hydrocephaly” (National Library of Medicine, 2013). Patients with achondroplasia are distinct in appearance. Obvious signs are the frontal bossing of the forehead, shortened limbs, short stature, hypotonia and bowed legs. Some joints can be hyperextended past the normal limits such as the knees. Other joints such as the hips and elbows have limited extension and rotation. (Conrad- Stoppler, 2012) Individuals with achondroplasia commonly suffer from fractures due to the nature of the disease. When the bones attempt to heal from the fractures the normal process is interrupted due to the abnormal gene. Instead of a fracture being replaced with a bony matrix of trabeculae that would be seen in a patient without achondroplasia, the bone heals by abnormal cartilage growth. This growth acts as padding between the bones fractured ends. This can cause complications such as reoccurring fractures of the afflicted bone or creating unstable joints in places that there should not be. The average height of a person diagnosed with achondroplasia is about 52 inches in males and 49 inches in females. According to the Guinness Book of World Records, the smallest person alive diagnosed with achondroplasia is Jyoti Amge of Nagpur, India who at 18 years old stands at just 24.7 inches tall. (Barrett, Dan, 2012) While most of the signs and symptoms of achondroplasia do not need medical intervention, there are many complications that need to be addressed promptly.

Complications that may arise in a patient with achondroplasia may be emergent, such as stenosis of the foramen magnum which can cause severe central apnea and death. The opening of the skull would have to be enlarged surgically to make room for the spinal cord and nerves that run through it. Women with achondroplasia characteristically have a smaller pelvis which could result in birthing complications and should plan for a cesarean section. A child with the disease may present with an extra large head which could result in bleeding of the brain during vaginal delivery due to cephalo-pelvic disproportion. Achondroplasia can also cause severe lordosis also called swayback. Patients may also develop a kyphosis or a hump in their thoracic spine and need surgery to relieve spinal stenosis, which is, “the most common medical complication of achondroplasia seen in adulthood” (Conrad-Stoppler, 2012). Limited only to treatment of specific symptoms makes caring for patient with achondroplasia difficult. Although a cure is not known at this time, there are experimental treatments on the horizon.

Several medications such as the Human Growth Hormone (HGH) are being considered for treatment. HGH has not yet been reported to have increased height in persons with achondroplasia. Limb lengthening is also an experimental and extremely controversial treatment within the world of achondroplasia. The ultimate goal of limb lengthening is to add several inches to a person’s height. This is done by “separating the long bone into two sections and these pieces of bone are then separated slightly and metal scaffolding braces the bones together” (Laberge, 2012) It has had good results in some studies but has caused complications in others. Because of its long term and painful treatment, limb lengthening is not preferred by most and is a matter of preference. Another option making a debut is a medication by BioMarin a research company in California. BioMarin believes they have developed a drug that may work in the same pathways of the brain that FGFR3 affects. BNM-11 has shown much promise in restoring normal growth to the limbs and areas of the body that are affected by achondroplasia, even changing facial structure on mice. The medication is now being tested on humans without achondroplasia to monitor the effects of its usage. “It is not known at this time what the long term affects are on humans or if it is safe in children as it is still in the testing phase” (Okenfuss, 2012). If this drug were to be approved as a successful treatment for achondroplasia it would be socially and personally life changing for achondroplasics worldwide.

There are many characteristics that are shared in patients with achondroplasia. Sometimes overlooked and most severely affected are the personal feelings of self esteem and self worth resulting from being different from most in society. Living in a world where everything is seemingly giant sized, where people stare because of your obviously small stature has taken a toll on many that suffer from dwarfism. Everything around us is built with the average sized person in mind. Those that suffer from dwarfism must adjust and adapt to a world made for taller people, making everything from driving a car to reaching the stove in the kitchen a monumental task. Over the years, accommodations have been developed to help aid people with achondroplasia such as cars with altered pedals and seats, houses that have been remodeled lowering cabinets, ceilings and doorways, as well as smaller appliances. These considerations have all been in an attempt to create normalcy and comfort which we are all entitled to regardless of stature. Feelings of discrimination in school or in the job market can also contribute to lower feelings of self worth. School adjustment and socialization may be difficult for children with achondroplasia. “Children with achondroplasia cannot participate in most competitive contact sports like football, soccer and lacrosse to “limit the risk of injury to the spinal cord at the cervical junction” (Pauli, 2012). There are many organizations out there today that support people with achondroplasia. One such organization is Little People of America. With over 6,000 members across the United States their “primary focus is to provide support, education, resources and advocacy for people with dwarfism” (Little People of America, 2012).

In conclusion, with achondroplasia’s genetic mutation being so newly discovered and also being only one of over 200 identified types of dwarfism it is not surprising to me that we have not yet found an effective treatment or cure. The symptomatic treatment of the patient with achondroplasia has to be the continued primary focus especially in childhood to ensure healthy growth and development within the parameters of the disease. Many agencies are available offering resources and education about achondroplasia. This is the first line of defense against social and emotional issues that can be prevented. We must maintain as a society, a commitment to treating all people equally regardless of size or differences. There is much yet to be learned about the genetic mutation that causes achondroplasia and promising medications that are undergoing trials as we speak. While there are many experimental medications and procedures that are being tested, it still stands that the patient and physician must remain diligent until a cure is found.

References:

Associated Press. (1994) Genetic Defect for a Type of Dwarfism Is Found. The New York Times. Retrieved from: http://www.nytimes.com/1994/07/31/us/genetic-defect-for-a-type-of-dwarfism-is-found.html

Barrett, D. (2012). Record holder q+a: Jyoti Amge, shortest woman. Retrieved from: http://www.guinnessworldrecords.com/news/2012/9/record-holder-qplusa-jyoti-amge-shortest woman-45050/

Conrad Stoppler, M. (2012). Achondroplasia. Retrieved from: http://www.medicinenet.com/achondroplasia/page2.htm

Mackie, E., Ahmed, Y., Tatarczuch, L., Chen, K., & Mirams, M. (2007) Endochondral ossification: how cartilage is converted into bone in the developing skeleton. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/17659995

Green, E. (n.d.). What is Achondroplasia? National Human Genome Research Institute. Retrieved from http://www.genome.gov/19517823

Laberge, M (2012) Limb Lengthening. Retrieved from: http://www.surgeryencyclopedia.com/La-Pa/Leg-Lengthening-Shortening.html

Little People of America (2012) What is LPA? Little People of America. Retrieved from: http://www.lpaonline.org/about-lpa

National Library of Medicine. (2011). Achondroplasia. A.D.A.M Medical Encyclopedia
[Internet]. Retrieved from: www.mcbi.nlm.nih.gov/pubmedhealth/PMH00025544/

Okenfuss, E. (2012) Emerging research and potential treatments in achondroplasia and other skeletal dysplasias. Little People of America. Retrieved from: http://www.lpaonline.org/research-and-treatments
Pauli, R. (2012) Achondroplasia. University of Wisconsin. Retrieved from: http://www.ncbi.nlm.nih.gov/book/NBK1152/

Wellness.com (2006)Achondroplasia. Wellness and Treatment. Retrieved from: http://www.wellness.com/reference/conditions/achondroplasia/prevention-and-treatment

References: Associated Press. (1994) Genetic Defect for a Type of Dwarfism Is Found. The New York Times. Retrieved from: http://www.nytimes.com/1994/07/31/us/genetic-defect-for-a-type-of-dwarfism-is-found.html Barrett, D Conrad Stoppler, M. (2012). Achondroplasia. Retrieved from: http://www.medicinenet.com/achondroplasia/page2.htm Mackie, E., Ahmed, Y., Tatarczuch, L., Chen, K., & Mirams, M Green, E. (n.d.). What is Achondroplasia? National Human Genome Research Institute. Retrieved from http://www.genome.gov/19517823 Laberge, M (2012) Limb Lengthening Little People of America (2012) What is LPA? Little People of America. Retrieved from: http://www.lpaonline.org/about-lpa National Library of Medicine Pauli, R. (2012) Achondroplasia. University of Wisconsin. Retrieved from: http://www.ncbi.nlm.nih.gov/book/NBK1152/ Wellness.com (2006)Achondroplasia