Achondroplasia is a bone growth disorder that results in disproportionate dwarfism due to a genetic mutation in the arms and legs, therefore making it the number 1 cause of dwarfism. Achondroplasia patients have an average height of less than 4 feet 6 inches (137 centimeters). According to Columbia University Medical Center, the condition affects roughly 1 in 25,000 live newborns (CUMC). It is common in both men and women. Despite the fact that the cause is a genetic mutation, only around one out of five children inherit the illness from their parents.
What is it?
Achondroplasia literally translates to "without cartilage formation”. However, in achondroplasia it’s not that there’s no formation of the cartilage but rather the process of turning it into bone (a process known as ossification), into long bones of the arms and legs doesn’t occur. This is caused by the mutations in the FGFR3 gene (Fibroblast growth factor receptor 3 gene). Your body is given instructions to create a Fibroblast growth factor receptor 3 proteiN, which is required for bone growth and maintenance by the FGFR3 gene. Since this gene is responsible for the growth of the skeleton, if the FGFR3 gene becomes mutated, the protein it codes for becomes overactive, preventing the growth of the skeleton. As a result, people with this illness have short limbs and a normal-sized torso.
Inheritance
Achondroplasia is inherited in an autosomal dominant pattern, which means that the mutated gene is a dominant gene and is located on one of the nonsex chromosomes known as the autosomes. This means that only one mutated gene is required to get the illness. Usually 80% of people with achondroplasia have parents with normal height, because the FGFR3 gene undergoes a new mutation. The remaining cases of achondroplasia are caused by one or more parents who carry the mutated FGFR3 gene and pass it on to their children. If two mutated copies of this gene are inherited from the parents, it leads to a severe type of achondroplasia that results in significant bone shortening and an underdeveloped rib cage. Usually, these babies are stillborn or pass away from respiratory failure soon after birth.
Symptoms
The age of onset for Achondroplasia is between the prenatal to newborn stages. Achondroplasia symptoms are primarily physical, not mental meaning that the level of intelligence isn’t affected. The symptoms of this syndrome are:
Bowing of legs (A long bone in the leg that is bent or has an irregular curve).
A small frame that is much shorter than typical for one's age and gender
Abnormally large and prominent forehead
Kyphosis (Round Back)
Limb undergrowth (Short limbs)
Thoracolumbar Kyphosis (Forward curvature of the upper back)
Underdeveloped area of the face between the forehead and upper jaw
Trident hand (Fingers in groups of three)
Newborns' delayed development in terms of sitting, crawling, and walking.
Most often, those who have this condition are able to lead regular lives, although with time, some may experience certain health problems, such as:
Back and leg pain.
Apnea (Breathing problems)
Obesity
Persistent ear infections.
Curved spine.
Hydrocephalus (Excess build up fluid in brain)
Obstructive sleep apnea
Diagnosis
Achondroplasia can be diagnosed during pregnancy or after the child is born. During an ultrasound, some achondroplasia symptoms can be seen such as an abnormally big head, hydrocephalus etc. Genetic tests could be conducted if the doctor suspects the fetus has achondroplasia, by examining a sample of amniotic fluid for the faulty FGFR3 gene. However, the majority of achondroplasia diagnoses are only made after the child is born, to ensure that diagnosis made earlier was correct . The doctor can diagnose the child after birth by examining his or her features. To determine the length of your infant's bones, the doctor can do an X-ray which could help support a diagnosis. Blood testing can also be conducted to check for the defective FGFR3 gene as well genetic testing can be used to validate a diagnosis and identify the genesis of the mutation.
Cure and Treatments
Other than controlling symptoms, there is no specific treatment or cure for achondroplasia. Following the diagnosis, growth progress is monitored by taking measurements of head circumference, weight, and height. Depending on the severity of the patient's illness, other therapies are also used aiming to reduce symptoms. For example, antibiotics are given for ear infections, and surgery may be necessary in severe spinal stenosis situations. There are other treatments that are currently being approved and tested such as a new dwarfism drug by BioMarin Voxogo (vosoritide). Children with achondroplasia over the age of five tested with the drug Voxzogo (vosoritide) has shown to promote linear growth by 6 centimeter each year . “An increase in the annual growth rate alone may have a positive effect on some patients’ quality of life. For other patients, now and in the future, our hope is that the altered bone growth throughout the body could ease such problems as sleep apnea and neurological, leg and back problems, and improve their quality of life,” quoted Julie Hoover-Fung, director of the Greenberg Center for Skeletal Dysplasia on the approval of the drug. Despite not yet having US or Canadian approval, the medication is legal in Thailand, Indonesia, Israel, Bahrain, Singapore, Nepal, and Hong Kong. There are still studies being conducted on whether the drug is safe for children below 5 years.
Achondroplasia is one of the most prevalent kinds of skeletal dysplasia - a condition that affects the bones and cartilage. Although the arms, legs, and face show the most obvious effects, almost all of the bones in the body are impacted. This condition's extensive effects may result in serious, progressively worsening, and lifelong problems but despite these issues, people with achondroplasia are nonetheless capable of leading happy and successful lives.
Written By: Tarleen Kaur Chhatwal
Edited By: Sakshi Deshpande
Glossary
Dwarfism - short stature that results from a genetic or medical condition.
Mutation - The changing of the structure of a gene, resulting in a variant form that may be inherited by the succeeding generations
Cartilage - A strong but flexible tissue that makes up a large portion of the skeleton during the early stages of growth.
Age of onset - The most common ages for symptoms of a disease to begin
Kyphosis - An increased front-to-back curve of the spine
Apnea - Sleep disorder in which breathing repeatedly stops and starts
Amniotic Fluid - The fluid surrounding the fetus in the womb
Bibliography
“Achondroplasia: MedlinePlus Genetics.” Medline Plus, medlineplus.gov/genetics/condition/achondroplasia/#inheritance. Accessed 29 July 2022.
“Achondroplasia - About the Disease - Genetic and Rare Diseases Information Center.” Genetic and Rare Diseases Information Center, rarediseases.info.nih.gov/diseases/8173/achondroplasia. Accessed 30 July 2022.
BioMarin Pharmaceutical Inc. “VOXZOGOTM (Vosoritide) | Our Products.” BioMarin, 2 Feb. 2022, www.biomarin.com/our-treatments/products/voxzogo.
“Achondroplasia: Symptoms, Treatment, Causes and Diagnosis.” Cleveland Clinic, 12 Oct. 2021, my.clevelandclinic.org/health/diseases/22183-achondroplasia.
“Achondroplasia.” Johns Hopkins Medicine, www.hopkinsmedicine.org/health/conditions-and-diseases/achondroplasia#:%7E:text=Achondroplasia%20is%20the%20most%20common,in%20the%20spine%20and%20skull. Accessed 30 July 2022.
Isenberger, Bill. “Encyclopedia of Rare Bone Diseases.” American Bone Health, 29 June 2022, americanbonehealth.org/rare-bone-disease-encyclopedia.
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