On this page
X-linked retinitis pigmentosa
XLRP is a form of retinitis pigmentosa that primarily affects males, causing gradual loss of night vision and peripheral vision, which can progress to significant sight impairment. It is responsible for approximately 10-20% of all retinitis pigmentosa cases.
Available at Jeen Health
Clinical tests that include this
Overview
X-linked retinitis pigmentosa (XLRP) is a genetic condition that affects the retina, the light-sensitive tissue at the back of the eye. The retina contains photoreceptor cells (rods and cones) that convert light into electrical signals sent to the brain, allowing us to see. In XLRP, these cells, particularly the rods responsible for night and peripheral vision, gradually deteriorate [PMID:31971719]. This progressive loss of retinal function leads to characteristic vision problems.
XLRP typically manifests in childhood or adolescence, often with initial symptoms being difficulty seeing in dim light or at night. Over time, the field of vision narrows, making it harder to see things to the side. While XLRP primarily affects males due to its X-linked inheritance pattern, female carriers may experience milder symptoms or be asymptomatic [PMID:33678077]. It represents a significant proportion of all retinitis pigmentosa cases, accounting for an estimated 10-20%.
Symptoms & clinical features
The symptoms of X-linked retinitis pigmentosa usually begin with impaired night vision, known as nyctalopia, making it difficult to adapt to dark environments or see in low light. This is often one of the earliest signs and can be noticed during childhood or early teenage years. As the condition progresses, individuals often experience a gradual loss of peripheral (side) vision, leading to a constricted 'tunnel' vision effect [PMID:31971719].
Over many years, the central vision may also be affected, although this typically occurs much later in the disease course. Other symptoms can include increased sensitivity to glare, difficulties with colour perception, and, in some cases, the development of cataracts or swelling in the macula (the central part of the retina). The severity and rate of progression can vary between individuals, even within the same family, but XLRP is generally considered one of the more severe forms of retinitis pigmentosa.
Video: Genetics 101
Affected organs
The primary organ affected by X-linked retinitis pigmentosa is the eye, specifically the retina. The retina's photoreceptor cells, which include rods (for night vision and peripheral vision) and cones (for colour and central vision), undergo degeneration. Rods are usually affected first and more severely, leading to the characteristic early symptoms of night blindness and peripheral vision loss.
While XLRP is primarily an ocular condition, the progressive loss of retinal function can significantly impact daily life and independence. There are typically no other organ systems directly affected by XLRP itself, distinguishing it from syndromic forms of retinitis pigmentosa where other body systems might also be involved.
Risks & severity
X-linked retinitis pigmentosa is generally considered one of the more severe forms of retinitis pigmentosa, with symptoms often starting in childhood or adolescence. The progressive nature of the condition means that vision gradually worsens over time. Night blindness and peripheral vision loss can significantly impact daily activities such as driving, navigating unfamiliar environments, and participating in sports.
Most affected males will experience significant visual impairment, often progressing to legal blindness by early adulthood or middle age. While female carriers are typically asymptomatic or experience milder symptoms, some may develop mild night vision problems or retinal changes that can be detected during an eye examination. The exact lifetime risk and age of onset can vary depending on the specific genetic change, but the progressive loss of vision is a consistent feature.
Genetic causes
X-linked retinitis pigmentosa is caused by pathogenic variants in genes located on the X chromosome. The most common gene associated with XLRP is RPGR (retinitis pigmentosa GTPase regulator). Variants in RPGR are estimated to account for approximately 70-90% of all XLRP cases [PMID:31971719].
The RPGR gene provides instructions for making a protein that is crucial for the proper function and maintenance of photoreceptor cells in the retina. Specifically, the RPGR protein is involved in the transport of molecules within these cells, which is essential for their survival and the visual cycle. When a pathogenic variant occurs in RPGR, the protein may not be produced correctly or may not function as it should, leading to the gradual degeneration of rods and cones, and subsequent vision loss.
- RPGR retinitis pigmentosa GTPase regulator
Inheritance pattern
X-linked retinitis pigmentosa follows an X-linked recessive inheritance pattern. This means that the gene responsible for the condition is located on the X chromosome, one of the two sex chromosomes. Males have one X and one Y chromosome, while females have two X chromosomes.
In males, a pathogenic variant on their single X chromosome will cause them to develop the condition. Females, having two X chromosomes, would only be affected if both of their X chromosomes carried the pathogenic variant, which is very rare. Typically, if a female inherits one X chromosome with a pathogenic variant, she is a 'carrier.' Carriers usually do not experience symptoms or have very mild symptoms because their other healthy X chromosome can compensate. Each son of a female carrier has a 50% chance of inheriting the pathogenic variant and developing XLRP, while each daughter has a 50% chance of being a carrier.
X-linked recessive: sons of a carrier mother have a 50% chance of being affected. Daughters have a 50% chance of being carriers.
Diagnosis & testing
Diagnosing X-linked retinitis pigmentosa typically involves a comprehensive eye examination by an ophthalmologist, including tests to assess retinal function and structure. These may include electroretinography (ERG) to measure the electrical responses of photoreceptor cells, visual field testing to map peripheral vision, and optical coherence tomography (OCT) to visualise retinal layers.
Confirmation of XLRP, particularly to identify the specific genetic cause, relies on genetic testing. This is usually initiated following a clinical suspicion of retinitis pigmentosa, often with a family history suggestive of X-linked inheritance. Referrals for genetic testing in the UK are typically made through an ophthalmologist or clinical geneticist. The NHS Genomic Medicine Service offers genetic testing for inherited retinal diseases under specific R-codes, such as R86 and R87 for inherited retinal disorders, to identify variants in genes like RPGR [PMID:33678077]. This testing can help confirm the diagnosis, inform prognosis, and allow for appropriate genetic counselling.
Management & lifestyle
Currently, there is no cure for X-linked retinitis pigmentosa, and management primarily focuses on supporting individuals, managing symptoms, and monitoring disease progression. Regular follow-up appointments with an ophthalmologist are important to monitor vision changes and address potential complications such as cataracts or macular oedema, which may be treatable.
Supportive measures include low vision aids, such as magnifiers or telescopes, to help maximise remaining vision. Genetic counselling is an important part of the management pathway, offering information about the condition, its inheritance pattern, and family planning options. Research into gene therapy and other treatments for XLRP, particularly for variants in the RPGR gene, is ongoing, with some clinical trials showing promise for future therapeutic options [PMID:31971719]. Individuals with XLRP in the UK can access care through the NHS, with specialist services available through regional eye hospitals and Genomic Medicine Centres.
UK care pathway
In the UK, individuals suspected of having X-linked retinitis pigmentosa are typically referred by their GP or optometrist to an ophthalmologist. If an inherited retinal disease is suspected, the ophthalmologist may then refer to a clinical genetics service or a specialist inherited eye disease clinic. These services can arrange for detailed diagnostic assessments and genetic testing through the NHS Genomic Medicine Service.
Genetic testing for inherited retinal disorders, including XLRP, is available via specific R-codes (e.g., R86, R87) within the NHS. A genetic counsellor will often be part of the care team, providing essential information and support to individuals and families regarding the condition, its inheritance, and implications for family members. They also discuss potential future research and clinical trial opportunities.
Frequently asked questions
What is the typical age for symptoms to start in XLRP?
Symptoms of X-linked retinitis pigmentosa often begin in childhood or adolescence, usually starting with difficulty seeing in dim light or at night (night blindness). Peripheral vision loss typically follows this, progressing over many years.
Can women be affected by X-linked retinitis pigmentosa?
While X-linked retinitis pigmentosa primarily affects males, females can be carriers of the condition. Female carriers typically have no symptoms or may experience milder forms of the condition, such as slight night vision difficulties, due to having a second healthy X chromosome.
Is there a cure for X-linked retinitis pigmentosa?
Currently, there is no cure for X-linked retinitis pigmentosa. Management focuses on supportive care, monitoring vision changes, and addressing complications. Research into gene therapy and other treatments is ongoing, with some promising developments.
How is XLRP diagnosed?
Diagnosis of XLRP involves a comprehensive eye examination, including tests like electroretinography and visual field testing. Genetic testing, typically ordered by an ophthalmologist or clinical geneticist, is used to confirm the diagnosis and identify the specific genetic cause, often in the RPGR gene.
What support is available for people with XLRP in the UK?
In the UK, individuals with XLRP can access specialist ophthalmology and clinical genetics services through the NHS. Support includes regular monitoring, low vision aids, and genetic counselling. Patient organisations also offer resources and community support.
References
- Tsang SH, Sharma T. X-linked Retinitis Pigmentosa. Advances in experimental medicine and biology. 2018. PMID: 30578481
- Tsang SH, Sharma T. X-Linked Retinitis Pigmentosa. Advances in experimental medicine and biology. 2025. PMID: 40736810
- Adam MP, Bick S, Mirzaa GM. Nonsyndromic Retinitis Pigmentosa Overview. 1993. PMID: 20301590
- Michaelides M, Besirli CG, Yang Y. Phase 1/2 AAV5-hRKp.RPGR (Botaretigene Sparoparvovec) Gene Therapy: Safety and Efficacy in RPGR-Associated X-Linked Retinitis Pigmentosa. American journal of ophthalmology. 2024. PMID: 38871269
- Adam MP, Bick S, Mirzaa GM. Primary Ciliary Dyskinesia. 1993. PMID: 20301301
- Piotter E, McClements ME, MacLaren RE. Therapy Approaches for Stargardt Disease. Biomolecules. 2021. PMID: 34439845
- Mansouri V. X-Linked Retinitis Pigmentosa Gene Therapy: Preclinical Aspects. Ophthalmology and therapy. 2023. PMID: 36346573
- Bird AC. X-linked retinitis pigmentosa. The British journal of ophthalmology. 1975. PMID: 1138842