Introduction

• Definition of Choroideremia
  • Choroideremia is a rare inherited eye condition that mainly affects those assigned male at birth¹ 
  • This condition can cause loss of vision and even blindness
  • Chiroideremia happens when a mutation occurs in the CHM gene, further leading to the deterioration of the choroid( which is a thin layer of tissue within the eye), the retinal pigment epithelium(a single layer of cells within the eye that acts as a barrier and regulator for photoreceptors which help project images in the brain), and lastly the retina (senses light and sends signals to the brain)
  • It affects 1 in every 50,000 men² 
• Gender and inheritance pattern³ 
  • Choroideremia follows a X-linked recessive inheritance pattern. 
  • When something is X-linked:
    • Humans have 23 chromosomes(carries genetic information providing instructions for the body)
    • These chromosomes are made up of pairs, these singular pairs are called alleles
    • You have sex chromosomes-this determines the sex you are born as.
    • Males assigned at birth have an X and a Y chromosome
    • Females assigned at birth have two X chromosomes 
    • Now since Choroideremia is an X-linked condition this means it is carried on the X chromosome
• These genes can further be labelled as ‘dominant’ or ‘recessive’
  • Recessive and X-linked means that one mutation from the father and one mutation from the mother must be inherited for individuals assigned female at birth to have severe symptoms
    • Those assigned male at birth will only have to inherit a mutated X chromosome from their mother for the possibility of severe symptoms
  • Dominant and X-linked means that only one mutation from one parent must be inherited for the individual to be affected
• Since it is recessive and X-linked this means that daughters tend to be what's known as a carrier, as they have inherited the mutation from one parent but they are not severely affected due to the other X Chromosome not being affected. However, they could pass on to their children
• Sons, although the statistic is rare, are more likely to be affected as they do not have the other X chromosome to compromise
• Purpose of outline
  • This article will explore the severity of the disease in those assigned male at birth
  • It will delve into the cause, presentation and implications of variability

Clinical features of choroidermia in males

Although symptoms vary among individuals these are the most commonly seen symptoms and how it progresses:⁴ 

From the ages 6-5:

• Difficulty seeing at night
• Difficulty with side vision
• Unable to see colours

Late childhood to adulthood:

• Narrowing of vision
• Central vision became worse at the age of 40⁵

Late adulthood:

• Potential blindness later on in life

Variability in disease severity

• Whether you are assigned female or male at birth:⁶
  • Those assigned female at birth tend to experience much milder symptoms than those assigned male at birth⁷ 
• Progression rate:⁸
  • The rate at which the retina degenerates has shown to vary among patients
• Severity:⁹
  • Some individuals assigned male at birth experience more severe symptoms than others 
• Late vs early symptoms beginning:⁶
  • Although symptoms start showing at the age of 10 but occasionally they can begin to show later on

Potential factors influencing variability 

There are 280 mutations that can cause CHM. However, there has been no evidence connecting the type of mutation and variation of symptoms but some evidence shows that the following may affect variability:¹⁰ 

• Genetic differences
  • Since mutations are not affecting the variability in this condition, other genetic differences may influence the severity
• Environmental and lifestyle factors
  • Varying light exposures can affect variability
  • Additional varying lifestyle choices may affect progression

However, there is a lack of information on what specifically could affect variability. 

Diagnostic and monitoring tools

Choroidermia tends to be misdiagnosed so it's important to go through multiple examinations to make sure the right treatment is applied.^4,11

• Ophthalmological examination- this is an exam for the eyes, checking your vision and eye health. This consists of :
  • Fundus photography- takes pictures of the back of the eye, specifically the choroid and retina
  • Fundus autofluorescence- lights up retinal pigment epithelium to see if it is damaged
  • Fluorescein Angiography-this is when dye is injected into the bloodstream to see the health of the blood vessels in the eyes
• Spectral domain optical coherence tomography-this examines your tissues, in case in your eyes
• If central vision begins to decline an individual should go to a vision specialist or vision rehabilitation clinic may be necessary for evaluation
• A medical geneticist may be useful as well to see the inheritance pattern and see the likelihood of an individual's children inheriting it

Implications of variability

This variability in chordaemia can can have some implications of various factors including:

• Affects prognosis¹²
  • As symptoms vary among individuals, it means that tracking is a lot harder and anticipating future vision loss
• Quality of life¹³
  • Due to the decline in vision it means daily activities can be difficult to fulfill
  • It can further affect the use of digital screens
  • There is a loss of independence
  • Additionally, it can lead to bad mental health
• Diagnosis⁶
  • As Choroidermia varies a lot and also shares a lot of similar symptoms to other conditions there tends to be a misdiagnosis which could lead to the wrong treatment being given

Current and emerging therapies 

There is no direct treatment for Choroidermia, however, there are certain steps and therapies that could be useful. For example, focusing on nutrition intake can benefit the eyes such as:¹⁴

• Antioxidant intake
• Omega-3

Gene replacement therapy has been trialled and shown to produce benefits in vision using AAV2-REP1 for gene augmentation.¹⁵

• Must be done with caution as it has also shown to have some negative results. 
• Another gene augmentation method uses 4D-110 

Stem cell therapy¹

• This is currently being used to restore tissues in the eye that are breaking down and improve vision

Genetic counselling

• Genetic counselling is great for families to understand how inheritance patterns works, whether their children will be affected and who is a carrier

FAQs

Can chorodermia be diagnosed early?¹⁶

• Diagnosis can be done through eye examinations and genetic testing
• Especially in individuals assigned male at birth as they tend to develop night blindness and side vision loss earlier on 

Should regular eye exams be done?⁴

• Regular eye checkups are important to monitor vision changes and eye health

Where can I find support?

• There are online support groups, foundations and charitable organizations for individuals and families affected by Chorodermia

What lifestyle adaptations can help manage Chorodermia symptoms?¹⁷

• Wear UV protection sunglasses 
• Diet rich in eye-health nutrients 
• Regular eye exams 
• Quit smoking 

Summary

Choredermia is a rare eye condition that primarily affects individuals assigned male at birth. It is caused by a mutation in the CHM gene which is located on an X chromosome. Since individuals assigned male at birth only have one X chromosome, a mutation in this gene normally leads to full expression of the disease. Those assigned female at birth tend to be carriers and experience much milder symptoms. The condition affects key parts of the eye that are used in capturing and processing light. 

A challenging aspect of Choredermia is the variability in the severity of the disease among individuals assigned male at birth. Some individuals experience night blindness from a young age and their vision rapidly declines, whereas others vision may remain functional throughout adulthood. Therefore, the rate at which side vision narrows and central vision is affected tends to differ from person to person. Some individuals assigned male at birth are still able to fulfill day-to-day activities, whereas others may go blind. 

Although there is not enough research to explain why severity and progression rate varies it has been demonstrated that it may not be to do with the type of mutation. However, other factors may influence variability such as the environment you are surrounded by, lifestyle choices and other genetic differences. 

Tools such as ophthalmological examination, optical coherence tomography and genetic examination are used to diagnose and monitor. This may be helpful for early detection, therefore, individuals can better plan their lives, seek treatment and become aware of clinical trials. Furthermore, they can receive a great amount of support and different therapies that may improve vision and mental health. 

In addition genetic counselling can be super helpful for families to understand the pattern of heredity and make any future decisions. As research advances, understanding and managing the variability in choroideremia will be key to improve outcomes and quality of life for those affected by the condition.