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Writer's pictureThe Rare360 Editorial Team
Nov 10, 20234 min read

Achondroplasia: Insights into Genetics, Diagnosis, and Treatment Options

Updated: Jan 16

Image depicting molecular genetics testing for Achondroplasia with test tubes and a report/form on a table.

Unlocking the Genetics of Achondroplasia and Its Prevalence

Achondroplasia is a rare bone growth condition that causes disproportionate dwarfism in affected individuals. Achondroplasia is primarily attributed to mutations in the FGFR3 gene, which provides instructions for making a protein involved in the development and maintenance of bone and brain tissue. While these mutations often occur spontaneously, they can also be inherited.


In the early stages of fetal development, a significant portion of the skeleton is composed of cartilage. Normally, this cartilage gradually transforms into bone. However, in cases of achondroplasia, the mutations in the FGFR3 gene disrupt this process, preventing much of the cartilage from converting into bone. As a result, individuals with achondroplasia experience shorter bone length, bone deformities, and reduced stature. Adult height for people with achondroplasia typically falls within the range of 42 to 56 inches.


The estimated prevalence of achondroplasia is approximately 1 in 15,000 to 1 in 40,000 live births.


Achondroplasia Symptoms and Long-Term Implications

One of the most characteristic features of achondroplasia is a shorter-than-average stature. Without treatment, the average adult male with achondroplasia stands at around 131 centimetres (4 feet, 4 inches) in height, while adult females typically average about 124 centimetres (4 feet, 1 inch). Achondroplasia symptoms appear differently among affected individuals, some of the common symptoms include:

  • Shortened arms and legs are a hallmark of achondroplasia. The upper arms and thighs are often more affected than the forearms and lower legs.

  • An enlarged head (macrocephaly), is characterized by a prominent forehead and a flattened nasal bridge.

  • Dental issues such as crowded or misaligned teeth.

  • Shorter fingers; the middle and ring fingers often diverge, giving the hand a trident-like appearance.

  • A pronounced and permanent sway in the lower back (lordosis) and bowed legs, typically developed during childhood.

  • An abnormal front-to-back curvature of the spine (kyphosis) and associated back pain.

  • Bowed lower legs and flat feet that are shorter and broader than average.

  • Reduced muscle tone and looser joints.

  • Frequent middle ear infections can lead to hearing loss.

  • Delayed developmental milestones; for example, walking may occur between 18 to 24 months of age, as opposed to the typical 12 months.


Other long-term implications of living with achondroplasia may include:

  • Obesity

  • Spinal stenosis involves a narrowing of the spinal canal that can compress the upper part of the spinal cord.

  • Difficulties in walking

  • Sleep apnea

  • Neurological impairment

  • Back and leg pain

Navigating the Diagnostic Path for Achondroplasia

The diagnostic process for a patient with achondroplasia typically involves the following steps:

  • Physical Examination: A complete medical history and physical examination are conducted after birth. During this evaluation, the physician will observe for classic achondroplasia traits, including shorter than average stature, shorter limbs, an enlarged head, and an average-sized torso.

  • Prenatal Detection: Achondroplasia can be detected during pregnancy through an ultrasound. This imaging technique is capable of detecting indicators such as hydrocephalus, characterized by an abnormally large head.

  • Genetic Testing: If achondroplasia is suspected, genetic tests may be ordered. These tests aim to detect the presence of a mutated FGFR3 gene, and they can be performed using either amniotic fluid (for prenatal diagnosis) or blood samples obtained after birth. In certain situations, DNA testing is now available before birth to confirm fetal ultrasound findings, particularly for parents who are genetically more likely to have a child with achondroplasia.

  • Radiographic Evaluation: X-ray examinations can be employed to measure the length of an infant's bones, aiding in the diagnostic process.

  • Ongoing Monitoring: Following a confirmed diagnosis, it is crucial for all children with achondroplasia to receive regular and attentive monitoring from a healthcare provider. This ongoing care helps in the early detection and management of any emerging health issues.

It's important to recognize that the diagnostic journey for each patient may differ based on their unique condition and medical history. The steps outlined here serve as a general guideline for the diagnostic process of achondroplasia.

Whole blood sample for Achondroplasia (FGFR3) 2 Mutation test to diagnosis of achondroplasia.

Addressing Achondroplasia: Treatment Options

Currently, there are various treatment options available to address symptoms and complications associated with achondroplasia. These treatment modalities encompass:

  • Medication: In cases of middle ear infections, antibiotics like Amoxicillin, Cephalexin, and Azithromycin may be prescribed to manage the condition.

  • Surgery: Surgical interventions may be considered, including procedures like laminectomy in severe instances of spinal stenosis and leg lengthening treatment.

  • Therapy: Growth hormone therapy is an option to augment a child's bone growth rate.

In a significant development, the U.S. Food and Drug Administration (FDA) granted approval to Voxzogo (vosoritide) in November 2021 for the enhancement of growth in children aged five years and older with achondroplasia, provided their growth plates remain open. This landmark approval marked the first medication specifically designed to target achondroplasia. The decision was based on an assessment of annualized growth velocity.


It's important to note that the most frequent adverse effects associated with vosoritide include injection site reactions, elevated blood alkaline phosphates, vomiting, joint pain, decreased blood pressure, and stomach aches.


Conclusion

In conclusion, achondroplasia reveals a complex interplay of genetics, diagnosis, and treatment options. This rare bone growth disorder, attributed to mutations in the FGFR3 gene, leads to distinctive symptoms such as shorter-than-average stature, enlarged heads, and skeletal deformities. The diagnostic journey involves meticulous steps, from physical examinations and genetic tests to ongoing monitoring, in order to acknowledge the unique traits and medical history of each patient.


While achondroplasia is not preventable, the medical landscape is continuously evolving to offer therapeutic solutions to those experiencing debilitating symptoms and comorbidities. Recent advancements, exemplified by the FDA approval of Voxzogo (vosoritide), signify a breakthrough for achondroplasia.


As we move forward, continued research, awareness, and medical innovations will undoubtedly shape a brighter future for individuals living with achondroplasia. Empowered by knowledge and advancements, the medical community stands poised to further improve the lives of those impacted by this condition, offering not just therapeutic solutions but also hope and support for a fulfilling life ahead.

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