Overview

Achondrogenesis is a rare genetic disorder that leads to abnormalities affecting bones and joints. It impairs bone development and leads to severe skeletal issues. The typical characteristics of this disorder are shorter limbs, a smaller chest and distinctive facial features, including a larger, more prominent forehead and smaller chin. There are numerous classifications of Achondrogenesis, all of which present skeletal abnormalities but with different disease severities and features: Type 1A, Type 1B, and Type 2.¹ Understanding the incidence and epidemiology of achondrogenesis is important for personal and professional guidance and advice in dealing with a life-limiting, rare disease diagnosis. Healthcare professionals can use knowledge gained via medical research of the disease to help explain to clients what the disease is. From there, this can help raise awareness of less common genetic disorders as well as shape management strategies, genetic counselling strategies or interventions if required.

What is achondrogenesis?

Achondrogenesis occurs as a result of mutations in genes that are involved in the production of collagen and the transport of sulphate ions. Collagen is crucial for the formation and structure of bone and skeletal tissue, while the transport of sulphate ions is necessary for cartilage development.² The disruption in collagen production and sulphate ion transportation affects the regular development and growth of bones and skeletal tissues, leading to the typical characteristics of shorter limbs, distorted spine, underdevelopment of the ribcage and chest and abnormalities represented by distinct facial features.³ 

Types of achondrogenesis

• Type 1A occurs as the result of mutations in the TRIP11 gene. This affects the production of collagen, resulting in skeletal abnormalities which can be lethal for newborn babies
• Type 1B occurs as the result of mutations in the SLC26A2 gene. This affects the regular transport of sulphate ions, resulting in disruptions to cartilage growth and development. Characteristics can be found similar to Type 1A, however, outcomes tend to be more severe, as this can lead to miscarriage, stillbirth or death in newborn babies
• Type 2 (most severe) occurs as a result of mutations in the COL2A1 gene. This also disrupts collagen production, however, it is more common than Type 1 achondrogenesis. The collagen production affected here disrupts the development of cartilage and connective tissue, resulting in skeletal abnormalities that are less severe than Type 1 achondrogenesis, however, the disease is still life-threatening 

The incidence of achondrogenesis

Incidence in relation to disease refers to the recorded number of cases diagnosed over a specific period of time. This is used to track the prevalence of disease occurring within a population. In 2020, the global prevalence of achondrogenesis was reported to be approximately 4.6 per 100,000 births.⁴ This also demonstrated that the incidence of disease was higher in areas including North Africa and the Middle East compared to Europe and America. Determining exact incident rates is challenging because of the rarity of achondrogenesis and lack of diagnosis. For example, the mother may miscarry before the unborn child can be diagnosed with the rare genetic condition.

There are numerous factors that could influence incidence rates. One of these is genetic predisposition,⁵ in which if both parents have a genetic mutation associated with achondrogenesis, there is an increased chance of their child having achondrogenesis. Alternatively, if the child receives one copy of a gene with a mutation associated with achondrogenesis, this could then be inherited by their children. Another factor may include isolated populations who may share blood-related genetics. This increases the likelihood of hereditary gene mutations being passed, matching to make a pair and resulting in rare genetic disorders such as achondrogenesis.⁶ 

Epidemiology of achondrogenesis

Epidemiology refers to the branch of science focusing on how diseases/disorders spread within a population. This helps researchers to understand how the disease works and is passed on, including risk factors that may be associated with the prevalence of achondrogenesis.  When researching the epidemiology of achondrogenesis, the epidemiology observed in studies tended to explore the likelihood of infants inheriting achondrogenesis-linked mutations as opposed to epidemiology in adults. This is because it is a genetic condition that is passed through the transfer of genes from parent(s) to the foetus. One study based on populations in Europe found that fathers aged over 34 were more likely to have children who carried genetic mutations related to achondrogenesis than younger fathers.⁷ This may suggest that a higher parenthood age could be a contributing risk factor associated with achondrogenesis in infants. 

Another study found that babies produced as a product of consanguinity (relationships between those who are related by genetics) were more likely to produce children with mutations that lead to severe abnormalities, such as those typical of achondrogenesis.⁸ Consanguinity has been proven to increase the risks of genetic mutations that can lead to disease.⁹ This is also backed up in another study that conducted genotyping on six individuals in a consanguineous family, whereby two out of six presented disorders similar to achondrogenesis affecting the limb.¹⁰ This suggests that consanguinity could also be a risk factor for inherited achondrogenesis. This is important to consider because North Africa has one of the highest percentages of consanguineous marriages/partnerships, and this is also where achondrogenesis was found to be more prevalent. 

Diagnosis and detection

Achondrogenesis can be diagnosed before birth (prenatal) or after birth (postnatal).

Prenatal techniques used for detecting achondrogenesis include ultrasound and genetic testing. In an ultrasound, the healthcare professional will observe for signs of skeletal abnormalities.¹¹ This can include both limb and spine development. Another technique that can be done is genetic screening tests.¹² This will enable the parents to find out the risk of their child inheriting genes that could result in characteristics typical of achondrogenesis. This can lead to emotionally and mentally difficult decisions for parents, as finding out their child has a high risk of or is likely to have severe, life-threatening skeletal abnormalities may lead to tough decisions such as termination of pregnancy. It can also lead to hard-to-hear news, such as low life expectancy for the baby either during pregnancy or postnatally.

Postnatal techniques for detecting achondrogenesis include clinical examination of the child after birth. Characteristics such as shorter limbs, skeletal abnormalities and distinct facial features can all be linked to disorders such as achondrogenesis. Genetic testing for mutations associated with each type of achondrogenesis can then help to identify the type of achondrogenesis due to mutations found through genetic screening.¹² This can also help identify it from other dysplasia disorders. 

Emotional and psychological impacts on families

An achondrogenesis diagnosis can have a significant emotional and psychological impact on families. When parents find out during pregnancy that their child is likely to have, or is at high risk of developing, skeletal abnormalities due to achondrogenesis, it can be an incredibly daunting time. All three types of achondrogenesis are associated with severe skeletal abnormalities and can be life-threatening. Some pregnancies may result in spontaneous abortion, where the body naturally induces a miscarriage, and the fetus does not survive. Other parents may need to discuss their options with a doctor regarding the continuation of the pregnancy. These discussions often involve the likelihood of the foetus surviving to birth, the expected quality of life for the child, and the child's life expectancy if they survive birth. In countries where it is permitted, some parents may choose a medically induced abortion, while others may decide to continue the pregnancy, knowing that their child will require specialised care for most of their life.

Dealing with the impacts of achondrogenesis

Once an unborn child or newborn has been diagnosed with achondrogenesis, there is currently no treatment or cure for the condition. The child’s life expectancy is typically very low, so it is critical for families to understand the disorder to help them cope with its impacts. Fortunately, there are patient organisations and counselling services available to support families and raise public awareness of achondrogenesis. These services, which can be accessed both online and in person, provide a base for people from all walks of life to discuss rare genetic disorders. This includes researchers, patients, doctors, and anyone impacted by or involved with conditions like achondrogenesis. If you or someone you know is dealing with this devastating diagnosis, it is crucial to speak with a healthcare professional who can offer guidance and recommend support resources to help navigate the emotional challenges.

Summary

Studying the incidence and epidemiology of achondrogenesis is crucial because there are still significant gaps in our understanding of the disease. Data on its prevalence is limited due to challenges in diagnosing and detecting the disorder before the loss of a child, which often occurs during pregnancy. Continued research and awareness of rare genetic disorders like achondrogenesis are necessary to improve our ability to identify individuals who carry genetic mutations associated with a higher risk of this rare condition. This knowledge can help in family planning by allowing potential parents to consider the risks to an unborn child and make informed decisions before pregnancy. Furthermore, educating those impacted by achondrogenesis about the disorder can provide vital support to affected families, helping them manage the challenges they may face.