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Familial exudative vitreoretinopathy
FEVR can lead to impaired vision, ranging from mild to severe, by disrupting normal blood vessel growth at the outer edges of the retina. It typically affects both eyes and presents differently in each individual.
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Overview
Familial exudative vitreoretinopathy (FEVR) is a rare genetic condition that primarily affects the retina, the light-sensitive tissue at the back of the eye. Individuals with FEVR have abnormal development of the blood vessels that supply the retina's outer edges. This improper development can cause blood vessels to leak, bleed, or even detach part of the retina, leading to a range of visual problems [PMID:24089270]. FEVR is present from birth, although symptoms may not appear until later in childhood or adulthood. The condition often affects both eyes, but the severity can differ between them.
Symptoms & clinical features
The symptoms of FEVR can vary widely, even among individuals within the same family, from very mild to severe. Some people may have no noticeable vision problems, while others may experience significant visual impairment. Common symptoms can include poor vision, particularly in one eye, or a reduced field of vision [PMID:24089270]. In more severe cases, individuals might experience strabismus (crossed eyes), nystagmus (involuntary eye movements), or leukocoria (a white reflection in the pupil). Retinal detachment, a serious complication where the retina pulls away from its normal position, can also occur and may lead to profound vision loss if not addressed [PMID:33996791]. Symptoms can progress over time, and regular eye examinations are important.
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Affected organs
FEVR primarily affects the eyes, specifically the retina and the vitreous humour (the gel-like substance that fills the eye). The condition disrupts the normal formation of blood vessels in the peripheral retina. This can lead to various complications within the eye, including the growth of abnormal fibrous tissue, haemorrhages (bleeding), and exudates (fluid leakage) within the retina and vitreous. In severe cases, the retina may detach, affecting overall eye structure and function.
Risks & severity
The severity of FEVR is highly variable, ranging from asymptomatic individuals with few retinal changes to those with severe vision loss due to retinal detachment. The condition can lead to progressive deterioration of vision in some cases. Complications such as retinal tears, retinal detachment, vitreous haemorrhage, and secondary glaucoma (increased pressure in the eye) represent significant risks. The exact age when symptoms become apparent can vary, with some individuals showing signs in infancy and others only in adulthood. Early detection and regular monitoring are crucial for managing potential complications and preserving vision [PMID:29017646].
Genetic causes
Familial exudative vitreoretinopathy is caused by changes (pathogenic variants) in several genes. Key genes associated with FEVR include FZD4, LRP5, and NDP. These genes are involved in the Wnt signalling pathway, which plays a critical role in the development of blood vessels, particularly in the retina [PMID:24089270].
Normally, the proteins produced by FZD4, LRP5, and NDP work together to ensure the correct growth and patterning of retinal blood vessels. When there is a pathogenic variant in one of these genes, this signalling pathway is disrupted. This disruption leads to the characteristic abnormal development of the retinal vasculature observed in FEVR, where blood vessels fail to reach the periphery of the retina and can form in an unorganised fashion.
- FZD4 frizzled class receptor 4
- LRP5 LDL receptor related protein 5
- NDP norrin cystine knot growth factor NDPThe NDP gene provides instructions for making the norrin protein, which is crucial for normal eye development, particularly retinal specialisation and blood vessel formation in the retina and inner ear.
Inheritance pattern
FEVR often follows an autosomal dominant inheritance pattern. This means that a person only needs to inherit one copy of a changed gene from either parent to develop the condition. If one parent has FEVR, there is a 50% chance with each pregnancy that their child will also inherit the condition. However, some individuals with an autosomal dominant form of FEVR may inherit the pathogenic variant from a parent who does not show symptoms (variable expressivity). In some cases, FEVR can occur due to a new (de novo) pathogenic variant in an individual with no family history of the condition. There are also rarer autosomal recessive and X-linked forms of FEVR.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
Diagnosing FEVR typically involves a comprehensive eye examination by an ophthalmologist, especially one with expertise in retinal disorders. This may include fundus photography, fluorescein angiography (a test using a dye to visualise blood vessels), and optical coherence tomography (OCT) to assess retinal structure. Suspicion of FEVR often arises from characteristic retinal findings, such as an avascular (blood vessel-free) peripheral retina and abnormal vessel branching [PMID:29017646].
Genetic testing is used to confirm a diagnosis of FEVR and identify the specific gene causing the condition. Referral to NHS Genomic Medicine Service for genetic counselling and testing may be considered, particularly if FEVR is suspected or a diagnosis needs confirmation for family planning. The relevant NHS National Genomic Test Directory R-codes for FEVR often fall under conditions affecting retinal development.
Management & lifestyle
Managing FEVR focuses on monitoring retinal health and addressing complications to preserve vision. Regular, detailed eye examinations are essential to detect any changes, such as retinal tears or detachment, early. Treatment options depend on the severity and specific complications. Laser therapy (photocoagulation) can be used to treat areas of poorly developed blood vessels or to seal leaks, preventing further progression of the disease [PMID:33996791]. In cases of retinal detachment or severe bleeding, surgical intervention may be necessary. Individuals are typically managed within the NHS by ophthalmologists specialising in medical retina conditions, with support from genetic counselling services.
While there is no cure, proactive management can often prevent severe vision loss. Lifestyle considerations generally revolve around protecting eye health and following clinical advice. Individuals with FEVR and their families can discuss management strategies and surveillance plans with their healthcare team. Family members of affected individuals may be advised to undergo screening eye examinations.
UK care pathway
In the UK, individuals suspected of having FEVR would typically be referred to an ophthalmologist for specialist assessment. If FEVR is clinically suspected and particularly if there is a family history, a referral to a Clinical Genetics service or a Genomic Medicine Centre may be made. Genetic counsellors play a key role in explaining the condition, inheritance patterns, and coordinating genetic testing via the NHS Genomic Medicine Service. The testing for FEVR is detailed within the NHS National Genomic Test Directory, typically under specific R-codes for inherited retinal diseases.
Frequently asked questions
Is FEVR always linked to a family history?
FEVR is often inherited, meaning it runs in families. However, it can sometimes occur due to a new genetic change in an individual, even if there's no previous family history of the condition. Genetic testing can help clarify the cause.
Can FEVR be cured?
Currently, there is no cure for FEVR. Management focuses on preventing vision loss by treating complications such as abnormal blood vessel growth or retinal detachment. Regular monitoring and appropriate interventions are crucial.
What is the likelihood of vision loss with FEVR?
The impact on vision is highly variable. Some individuals may have excellent vision with only minor retinal changes, while others can experience significant vision impairment, especially if complications like retinal detachment occur. Early intervention can often help preserve vision.
If I have FEVR, will my children also have it?
If you have an autosomal dominant form of FEVR, there is a 50% chance with each child you have that they will inherit the condition. Genetic counselling can provide personalised risk assessments and discuss reproductive options.
How often should someone with FEVR have their eyes checked?
The frequency of eye examinations for individuals with FEVR depends on the severity of the condition and the presence of any complications. Your ophthalmologist will advise on a personalised schedule, which may involve annual or more frequent check-ups, especially for children.
References
- Tao T, Xu N, Li J. Ocular Features and Mutation Spectrum of Patients With Familial Exudative Vitreoretinopathy. Investigative ophthalmology & visual science. 2021. PMID: 34860240
- Sızmaz S, Yonekawa Y, T Trese M. Familial Exudative Vitreoretinopathy. Turkish journal of ophthalmology. 2015. PMID: 27800225
- Tauqeer Z, Yonekawa Y. Familial Exudative Vitreoretinopathy: Pathophysiology, Diagnosis, and Management. Asia-Pacific journal of ophthalmology (Philadelphia, Pa.). 2018. PMID: 29633588
- Gilmour DF. Familial exudative vitreoretinopathy and related retinopathies. Eye (London, England). 2015. PMID: 25323851
- Ebert EM, Mukai S. Familial exudative vitreoretinopathy. International ophthalmology clinics. 1993. PMID: 8325737
- Luvisi JR, Blair K. Familial Exudative Vitreoretinopathy (FEVR). 2025. PMID: 40334027
- Criswick VG, Schepens CL. Familial exudative vitreoretinopathy. American journal of ophthalmology. 1969. PMID: 5394449
- Huang L, Lu J, Wang Y. Familial Exudative Vitreoretinopathy and Systemic Abnormalities in Patients With CTNNB1 Mutations. Investigative ophthalmology & visual science. 2023. PMID: 36790797