Choroideremia

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Choroideremia is a condition characterized by progressive vision loss that mainly affects males. The first symptom of this condition is usually an impairment of night vision (night blindness), which can occur in early childhood. A progressive narrowing of the field of vision (tunnel vision) follows, as well as a decrease in the ability to see details (visual acuity). These vision problems are due to an ongoing loss of cells (atrophy) in the specialized light-sensitive tissue that lines the back of the eye (retina) and a nearby network of blood vessels (the choroid). The vision impairment in choroideremia worsens over time, but the progression varies among affected individuals. However, all individuals with this condition will develop blindness, most commonly in late adulthood.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the CHM gene cause choroideremia. The CHM gene provides instructions for producing the Rab escort protein-1 (REP-1). As an escort protein, REP-1 attaches to molecules called Rab proteins within the cell and directs them to the membranes of various cell compartments (organelles). Rab proteins are involved in the movement of proteins and organelles within cells (intracellular trafficking). Mutations in the CHM gene lead to an absence of REP-1 protein or the production of a REP-1 protein that cannot carry out its protein escort function. This lack of functional REP-1 prevents Rab proteins from reaching and attaching (binding) to the organelle membranes. Without the aid of Rab proteins in intracellular trafficking, cells die prematurely.

The REP-1 protein is active (expressed) throughout the body, as is a similar protein, REP-2. Research suggests that when REP-1 is absent or nonfunctional, REP-2 can perform the protein escort duties of REP-1 in many of the body's tissues. Very little REP-2 protein is present in the retina, however, so it cannot compensate for the loss of REP-1 in this tissue. Loss of REP-1 function and subsequent misplacement of Rab proteins within the cells of the retina causes the progressive vision loss characteristic of choroideremia.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Choroideremia is inherited in an X-linked recessive pattern. The CHM gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

In X-linked recessive inheritance, a female with one mutated copy of the gene in each cell is called a carrier. She can pass on the altered gene, but usually does not experience signs and symptoms of the disorder. Females who carry a CHM mutation may show small areas of cell loss within the retina that can be observed during a thorough eye examination. These changes can impair vision later in life.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The prevalence of choroideremia is estimated to be 1 in 50,000 to 100,000 people. However, it is likely that this condition is underdiagnosed because of its similarities to other eye disorders. Choroideremia is thought to account for approximately 4 percent of all blindness.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal electroretinogram · Very frequent (99-80%)

Any abnormality of the electrical responses of various cell types in the retina as measured by electroretinography.

Abnormality of retinal pigmentation · Very frequent (99-80%)

Any deviation from the normal pigmentation of the retina.

Myopia · Very frequent (99-80%)

An abnormality of refraction characterized by the ability to see objects nearby clearly, while objects in the distance appear blurry.

Nyctalopia · Very frequent (99-80%)

Inability to see well at night or in poor light.

Visual impairment · Very frequent (99-80%)

Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.

Choroideremia · Frequent (79-30%)

Well-defined, pale patches in the fundus.

Constriction of peripheral visual field · Frequent (79-30%)

An absolute or relative decrease in retinal sensitivity extending from edge (periphery) of the visual field in a concentric pattern. The visual field is the area that is perceived simultaneously by a fixating eye.

Peripheral visual field loss · Frequent (79-30%)

Loss of peripheral vision with retention of central vision, resulting in a constricted circular tunnel-like field of vision.

Other findings in the same source

From: Orphanet

Additional reported features include Progressive visual loss (Frequent (79-30%)); Abnormal fundus autofluorescence imaging (Occasional (29-5%)); Chorioretinal atrophy (Occasional (29-5%)); Choroidal neovascularization (Occasional (29-5%)); Color vision defect (Occasional (29-5%)); Macular edema (Occasional (29-5%)); Posterior subcapsular cataract (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Choroideremia is Ophthalmology, with a ophthalmologist as the relevant type of clinician. Ophthalmologist; paediatric services for children as appropriate.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which part of the eye or visual pathway is affected?
• What change in vision requires immediate contact with the eye service?
• What are the aims and alternatives of any proposed eye treatment?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Choroideremia. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.