Achondroplasia is a genetic disorder and the most common form of dwarfism that is characterized by disproportionate short stature, a prominent forehead, midface hypoplasia, and trident hands (Harada et al., 2017, p. 874). According to a 2012 Genetics Home Reference article titled “Achondroplasia,” the skeleton is mainly composed of cartilage during early life, and sometimes this cartilage doesn’t fully convert into bone in long bones such as the femur or tibia. This prevents bones from growing, thus leading to shorter limbs. Patients face other symptoms associated with achondroplasia, which will be explained later on in this paper along with the causes and current treatments. While no definite cure exists for achondroplasia, scientists continue to do research and conduct studies in an effort to develop the best treatment for patients with this bone disorder.
Causes and Contributing Factors
Achondroplasia is a fairly rare condition that affects about one in every 15,000 to one in every 35,000 births (Zhou & Pauli, 2018). Both males and females are affected in equal numbers. Alan (2016) explains that achondroplasia is a genetic disorder that is caused by mutations in a gene called Fibroblast Growth Factor Receptor 3 (FGFR3). When FGFR3 proteins are mutated, they become overly active and cause interferences with skeletal development. They impede cartilage growth resulting in shorter bones. According to Zhou and Pauli (2018), achondroplasia is caused by a spontaneous mutation eighty percent of the time. These spontaneous mutations can be the result of having a father that is advanced in age. The other twenty percent of the time, it is inherited by a parent with the same mutation in the FGFR3 gene. A March of Dimes article titled “Achondroplasia” published in 2013 explains that there is a fifty percent chance the offspring may inherit the gene if one parent has it. If both parents have the condition, then there is still a fifty percent chance the child will have it, a twenty-five percent chance it won’t have it, and a twenty-five percent chance the child will develop a fatal form of achondroplasia called homozygous achondroplasia.
Symptoms
Achondroplasia has a large variety of signs and symptoms. Patients with this disorder are notoriously short in stature. Adults typically don’t grow past four feet and a half. The average adult height for men with achondroplasia is four feet and four inches, while the average for women is four feet and one inch (Genetics Home Reference, 2012). People with achondroplasia have macrocephaly, which is having an abnormally large head. They also have trident hands meaning they have short fingers and their ring finger and middle finger diverge. This makes it their hands look like a trident because of the three-pronged appearance. As stated in Kieffer’s 2018 article title “Achondroplasia,” it is common for people with achondroplasia to have a flattened nasal bridge, crowded or misaligned teeth, and flat feet. They also have a curved lower spine. This condition is called lordosis. While people with achondroplasia usually have normal intelligence, they often experience developmental milestones at a slower rate. For instance, it can take a child with achondroplasia up to two years to learn to walk. Kieffer also talks about neurological deficits achondroplasia patients can be faced with. This includes hydrocephalus, which can cause headaches, irritability, lethargy, and vomiting. The Genetics Home Reference article published in 2012 informs that there are many health issues associated with achondroplasia. Obesity, ear infections, breathing problems, kyphosis, spinal stenosis, and back pain are examples of this. Evidently, achondroplasia patients face several health problems that go beyond their height.
Current Treatments
As of right now, there is no cure for achondroplasia, but there are several types of treatments available to patients for some of the symptoms of the disorder. “When symptoms are identified and acted upon in a timely manner, modern medial and surgical care allows achondroplastic children to grow up with intellectual and social capacities equal to that of other children” (Keiffer, 2015). Zhou and Pauli (2018) list various treatments for many problems arising from achondroplasia. For example, managing middle ear dysfunction by using ear tubes or treating sleep apnea by performing an adenotonsillectomy are ways to improve the lifestyle of someone with achondroplasia. Alan (2016) explains that many people have used human growth hormone and that is has successfully increased bone growth rate. While this helps patients gain some length, this hormone unfortunately doesn’t result in normal height. Surgery is also an option for those who have specific skeletal deformities. Bone lengthening procedures are another possible course of action. However, these procedures can be time-consuming and may lead to serious complications. When executed effectively, a bone lengthening procedure can result in a significant increase in height and can even allow a person to have near-normal stature and proportions. Even though there is currently no known cure for achondroplasia, scientists continue to research and work towards finding one. “Scientists are exploring ways to create alternate growth factors which can bypass the missing receptor and lead to normal bone growth” (Alan, 2016).
Current Research: Long-Term Growth Hormone Treatment
Over the past several years, scientists have formulated different strategies and ideas to treat achondroplasia. Not all have been successful, but it’s evident that these endeavors can provide a framework for future research and potential discoveries. A study conducted by Daisuke Harada and several other Japanese scientists aimed to evaluate the gain in final height of achondroplasia patients with long-term growth hormone treatment. This longitudinal study began in 2012 and yielded its final results in 2017. It included both male and female participants. Fifty-two achondroplasia patients had been enrolled in the study, but the final height data had only been obtained from twenty-two patients. Within this final group of people, there were three groups of patients treated in different ways to determine the effect of certain combinations of treatments. Seven patients were treated solely with long-term growth hormone. Nine people were given growth hormone and also underwent tibial lengthening. Six patients underwent femoral lengthening, tibial lengthening, and were given growth hormone. Patients went through physical and blood/biochemical examinations every 3 or 4 months. After years of recording data, Harada’s team was able to see an average final height increase of 3.5 centimeters for males and 2.8 centimeters for females that only received growth hormone. Patients that underwent tibial lengthening in addition to receiving growth hormone saw a ten centimeter increase in final height for males and a 9.8 centimeter increase for females. Patients that underwent tibial lengthening, femoral lengthening, and received growth hormone saw a 17.2 centimeter increase for males and a 17.3 centimeter increase for females (Harada et al., 2017, p. 876). It was concluded that long-term growth hormone treatment contributed to 2.6 percent of final adult height in male achondroplasia patients and 2.1 percent for females. While this may not seem like a monumental change, it did have an impact on achondroplasia patients and may allow other scientists to work off of their findings and discover better ways to treat this disorder. This study was funded by a grant from the Foundation for Growth Science.
Current Research: Soluble FGFR3 Therapy
Another study conducted by Celine Saint-Laurent and several other contributors was published on April 13, 2018. The study focused on finding a way to prevent the development of obesity in patients with achondroplasia. Obesity is a common complication in achondroplasia patients; an estimated fifty percent of children with achondroplasia experience obesity. This can lead to major health issues, so the purpose of the study was to find a way to stop the development of obesity and improve the lifestyle of those with achondroplasia. They began by using soluble FGFR3 on mice carrying the achondroplasia mutation. These mice displayed human-like symptoms associated with achondroplasia. When treated with soluble FGFR3 and observed over a given period of time, the mice demonstrated restored bone growth. The therapy also prevented metabolic deregulations and the development of obesity (Saint-Laurent et al., 2018, p. 3). They believed that if a similar procedure were to be applied to humans, the results would be just as successful. This study gives a promising outlook for humans and how soluble FGFR3 therapy would affect bone growth in people with achondroplasia. Saint-Laurent and her team were able to conclude that soluble FGFR3 therapy, if administered early on, would target bone growth and prevented the development of obesity. This study created a strong foundation for other scientists to build up from, and it will positively impact achondroplasia patients’ lifestyle in the future.
Current Research: Meclozine Treatment
A study conducted by Masaki Matsushita and other Japanese scientists was initiated to determine whether or not meclozine, an anti-histamine drug, could be a therapeutic agent for treating achondroplasia as well as other disorders associated the FGFR3 gene mutations. They found that meclozine enhanced embryonic tibia growth and that it could potentially suppress abnormally activated FGFR3 genes signaling in achondroplasia. A meclozine-treated embryonic tibia was compared to a control embryonic tibia. The meclozine-treated tibia had increased longitudinal growth of the bone and the cartilage. They also discovered that meclozine “facilitates chondrocyte proliferation and mitigates loss of extracellular matrix” (Matsushita et al., p. 2). Cell growth increased tremendously when human chondrosarcoma cells with FGFR3 mutants were treated with meclozine. Cellular proliferation had previously been suppressed, but the meclozine managed to increase cell growth. Meclozine can potentially be used as a therapeutic agent for achondroplasia patients. With this research, there’s a higher possibility of scientists finding something to “shut-down” mutated FGFR3 genes, thus getting us a step closer to treating achondroplasia.
Conclusion and Future in Achondroplasia Research
Achondroplasia has had an impact on hundreds of people around the world. Every passing year brings new research and discoveries regarding this bone disorder, yet no cure exists for it. In most cases, achondroplasia occurs spontaneously and there is nothing anyone can do to prevent it. Some of the symptoms relating to achondroplasia can be medical problems of their own and only worsen patients’ lifestyles. Nevertheless, many treatments are available to help patients manage achondroplasia, and people are trying to find ways to improve these people’s way of life. Despite the fact that several years of research on achondroplasia hasn’t led to finding a cure, scientists continue to put forth all of their effort in an attempt to come one step closer to making a lasting impact on patients with achondroplasia. Even though no one has found an actual cure, the research and all of the studies concerning this disorder have provided a valid starting point for other scientists. Researchers are able to move forward because of the discoveries that have already been made. Considering the amount of information that is now known about achondroplasia and the advances that have been made, it is evident that future scientists will make huge strides in helping people with achondroplasia. Regardless of whether or not a cure is found later on, there is no doubt that achondroplasia patients will be better off in the generations to come.
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