How Does Achondroplasia Affect Life Expectancy, And What Complications Are Common In This Form Of Dwarfism?

Achondroplasia is a disorder of bone formation, and it’s the most common cause of short stature (dwarfism). It’s estimated that one in 10,000-35,000 babies are born with this genetic condition, the main features of which are short arms and legs. 

How and why does achondroplasia develop?

The word achondroplasia translates to “without cartilage formation”. Contrary to what the name suggests, people with achondroplasia have normal cartilage development. The developmental difference occurs in the bone-making process, instead.

The majority of bone formation happens while a baby is still a fetus. Bones that build our skull, jaw, and hips develop from connective tissue called mesenchymal tissue. This process is undisturbed in people with achondroplasia. 

Long bones, like the ones that form our limbs, start from cartilage. Like most processes in the body, this one is tightly regulated by specific proteins that dictate just how many cartilage cells should be turned to bone cells, and how many should remain cartilage. 

But when there’s a mutation in the gene coding for FGTR3, which is the case in achondroplasia, chondrocytes make too much of this protein, and start signaling the body to stop bone formation before enough bone is formed. That’s why the long bones of people with achondroplasia end up being shorter than typical. 

How is achondroplasia inherited?

We inherit chromosomes (packages of DNA) in pairs: one copy from the mother, and the other from the father. Achondroplasia is inherited in a so-called autosomal dominant manner. It’s called dominant because one mutated copy of the gene will cause the disorder even though the other copy is normal. However, if a child inherits two mutated copies of the gene, death usually happens during the first year of life, with few exceptions. 

This means that adults with achondroplasia have one normal and one mutated gene for FGTR3. They have an equal chance of passing a normal or a mutated gene to their offspring, meaning there’s a 50 percent chance of inheriting achondroplasia from parents with this condition. However, the majority of cases don’t come from parents with the disorder.

In 80 percent of achondroplasia cases, the parents had two normal copies for the gene, but a change happened due to a mutation in the father's sperm cells. That’s called a “de novo” mutation. The chance of this mutation increases with a father’s age.

How does achondroplasia affect your lifespan?

While trying to find about premature death in achondroplasia you might come across some contradictory information. The reason is that not enough studies have been done on this subject, and the studies we do have are either old or based on a small sample.

In particular, research shows:

• An increased risk of sudden death in children with achondroplasia younger than four years. While some causes remain unknown, over half of them happen due to brain-stem compression. 
• The risk of heart disease is significantly increased among 5-24 year old patients. One study found that 10 out of 17 deaths in this age group were due to cardiovascular events.
• Increased risk of respiratory diseases contributes to overall deaths

Complications can happen, but this doesn’t mean that every achondroplasia patient will die early. It depends on the person's risk factors, and how good their medical care and screening is. Monitoring and following the condition regularly can help improve health outcomes.

Which complications can affect the lifespan of achondroplasia patients?

While we still haven’t identified all risk factors, we know what can go wrong and why, which is one step closer to figuring out how to prevent complications of achondroplasia. You can’t influence certain inborn characteristics, but you can minimize risk factors for specific complications like cardiovascular diseases. 

First, it’s important to be aware of possible complications and look out for the symptoms.

Complications typical for infants and children with achondroplasia include:

• Hydrocephalus. Hydrocephalus literally translates to “water head”. The central nervous system (brain and spinal cord) is cushioned in a special fluid called cerebrospinal fluid (CSF) that’s constantly circulating through it. It provides protection for these sensitive parts of the body. Due to a narrowing of the spinal canal, the CSF can get trapped and unable to move in and out of the skull, causing fluid buildup. This puts pressure on the brain and can cause enlarged head, vomiting, lethargy, headaches, and irritability. 
• Hypotonia (weak muscle tone). This can cause delay in developing motor skills.
• Spinal cord compression or vertebral artery compression. These can be particularly dangerous and cause problems with breathing like central apnea.

Complications of achondroplasia linked to a shortened lifespan in adults include:

• Obesity. It’s not completely clear why achondroplasia patients are prone to obesity, but it’s known to be a common complication. One study found that 25.8 percent of children were obese, while this number is even higher in adults. Obesity is a risk factor for a myriad of health problems.
• Sleep apnea (and other respiratory problems). Breathing disturbances are common among the ACH population, and the most common form is interruptance of breathing or apnea.
• Cardiovascular diseases. As mentioned, cardiovascular diseases are the main cause of death among young achondroplasia patients. Obesity is a well documented risk factor for cardiovascular disease.

Do age and sex play a role?

• Both males and females have about the same risk of developing complications, indicating that sex is not a risk factor.
• Sudden death is most common in the first year of life, with some studies indicating that the risk of death is increased by 7 percent compared to the general population. However, even though some achondroplasia complications are associated with certain age groups (infancy to four year olds, five to 24 year olds), the complications are not caused by age, but by inborn differences. For example, whether there’s spinal cord suppression and the size of opening in the skull called foramen magnum are directly linked to fatal outcomes. 

Are there ways to prevent complications of achondroplasia?

Some complications can’t be prevented, but monitoring for them and treating them early can lower your risk of long-term adverse consequences with achondroplasia. That’s why a good medical team that will monitor the person regularly throughout life and especially through childhood is important. Even any achondroplasia complications that do happen can be prevented from becoming fatal outcomes.

Risk factors you can influence include the following:

• Obesity. Preventing obesity is extremely important since people with achondroplasia already have a predisposition for cardiovascular diseases and sleep apnea. Both of those conditions can be worsened by obesity and can be life-threatening. Parents are advised to weigh their children and adjust the diet accordingly starting from the earliest age. This needs to be monitored through the whole life.
• Diagnosing, monitoring and treating sleep apnea. Babies with achondroplasia should have a detailed neurological assessment including MRI or CT to determine the size of foramen magnum and other possible complications. But it’s also important to do sleep studies and determine if there’s sleep apnea. Apnea can sometimes lead to fatal outcomes, but there are measures that can be taken to ease this condition, which is why it’s important that it’s diagnosed and regularly followed.
• Minimizing other risks of cardiovascular diseases. The advice is the same as for the general population, and other than controlled diet includes physical activity and avoiding smoking.
• A special emphasis on mental health. Mortality studies showed that many premature deaths in people with achondroplasia were due to drug overdose, accidental deaths, and suicide. It’s therefore thought that achondroplasia is a risk for self-injurious behaviors. Achondroplasia patients report depression, poor self-image, low self-esteem, and chronic pain. Many feel out of place, living in a world that wasn’t made for them, but for the average-sized.