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Congenital fibrosis of extraocular muscles
CFEOM affects the muscles responsible for controlling eye movement, causing the eyes to be fixed in certain positions and making it difficult to move them normally. This can affect vision and typically manifests from birth.
Overview
Congenital fibrosis of extraocular muscles (CFEOM) refers to a group of rare conditions that are present from birth and affect the muscles around the eyes. Individuals with CFEOM typically have difficulty moving their eyes in certain directions, often resulting in the eyes being fixed in a specific position, such as looking downwards and inwards [PMID:17918072]. This primary characteristic is due to the abnormal development and function of the extraocular muscles, which are responsible for eye movement. The condition does not typically worsen over time, as it is a fixed developmental issue.
CFEOM is considered a rare disorder, though the exact number of people affected in the UK is not well established. It is present from birth, meaning affected individuals are born with the condition. The impact of CFEOM can vary widely among individuals, from mild difficulties with eye movement to more significant limitations that might affect daily activities and visual processing.
Symptoms & clinical features
The primary symptom of CFEOM is restricted eye movement, which can manifest in several ways. Typically, one or both eyes may be fixed in an abnormal position, often looking down and out, or down and in [PMID:15610816]. This limitation in eye movement means individuals cannot move their eyes fully in all directions.
An individual with CFEOM may compensate for their inability to move their eyes by adopting an abnormal head posture, such as tilting their head or turning their face to see clearly. This is a common adaptive behaviour to achieve binocular vision (using both eyes together) or to maximise their field of view. Some individuals may also experience ptosis, which is a drooping of the upper eyelid, further affecting vision. Strabismus, where the eyes are not aligned correctly, is another common feature of CFEOM.
Depending on the severity and specific type of CFEOM, these symptoms can affect depth perception and visual acuity (sharpness of vision). The degree of visual impairment varies, and some individuals may not have significant vision loss. However, the limited eye movement often creates practical challenges.
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Affected organs
CFEOM primarily affects the extraocular muscles, which are the six muscles surrounding each eye that control its movement. In CFEOM, these muscles are underdeveloped or improperly formed, leading to a fibrous, non-functional tissue instead of healthy muscle [PMID:10091398]. This abnormal development directly restricts the eye's ability to move freely.
While the condition mainly impacts these eye muscles, complications can indirectly affect other parts of the visual system, such as the eye itself, due to prolonged abnormal alignment. The brain's visual processing centres may also be affected by the unusual visual input received from the misaligned eyes.
Risks & severity
The severity of CFEOM can vary considerably, even within families. Some individuals may experience only mild limitations in eye movement, while others have severely restricted movement, with the eyes fixed in a particular gaze. The condition is congenital, meaning it is present from birth and typically does not progress or worsen over time.
There is a potential risk of amblyopia (sometimes called 'lazy eye') if one eye has significantly poorer vision or is more misaligned than the other, as the brain may favour the stronger eye. Early detection and management are important to mitigate this risk. In some forms of CFEOM, other neurological features may be present, however, these are generally rarer and depend on the specific genetic cause.
Genetic causes
CFEOM is a genetic condition, meaning it is caused by changes in specific genes. One gene commonly associated with a form of CFEOM is TUBB3. The TUBB3 gene provides instructions for making a protein called beta-tubulin class III [PMID:17918072]. This protein is a crucial component of microtubules, which are structural elements found within cells.
Microtubules are particularly important in the development and function of nerve cells. Pathogenic variants in the TUBB3 gene disrupt the normal formation of these microtubules, especially in the cranial nerves that control eye movement [PMID:17918072]. This disruption leads to the abnormal development or incorrect wiring of the nerves and muscles responsible for moving the eyes, resulting in the characteristic restricted eye movements observed in CFEOM.
- TUBB3 tubulin beta 3 class III
Inheritance pattern
CFEOM can be inherited in different ways, depending on the specific genetic cause. Some forms follow an autosomal dominant inheritance pattern, while others are autosomal recessive.
In autosomal dominant inheritance, only one copy of an altered gene is needed to cause the condition. This means that if one parent has the condition, there is a 50% chance with each pregnancy that their child will also inherit the altered gene and develop CFEOM. In autosomal recessive inheritance, an individual must inherit two altered copies of the gene (one from each parent) to develop the condition. If both parents carry one altered copy, they are typically unaffected, but there is a 25% chance with each pregnancy that their child will inherit two altered copies and be affected.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
The diagnosis of CFEOM is typically established based on characteristic clinical findings of restricted eye movement present from birth. An ophthalmologist or paediatrician may suspect CFEOM based on a clinical examination. Imaging studies, such as magnetic resonance imaging (MRI) of the brain and orbits, can be used to visualise the extraocular muscles and nerves, confirming their abnormal development or absence in affected individuals [PMID:10091398].
Genetic testing is key to confirming the diagnosis and identifying the specific gene variant responsible. This is usually coordinated through clinical genetics services within the NHS. Genetic testing for CFEOM can be accessed via the NHS Genomic Medicine Service (GMS) through specific R-codes, such as R253 Congenital ophthalmoplegia or R89 Cranial neuropathy, depending on the specific clinical presentation. A referral to a clinical geneticist is typically made by a specialist, such as an ophthalmologist or neurologist, to arrange appropriate genomic testing and genetic counselling.
Management & lifestyle
While there is currently no cure for CFEOM, management primarily focuses on alleviating symptoms and improving visual function. Management strategies are individualised based on the severity of eye movement limitation and any associated symptoms.
Corrective lenses may be prescribed to address any refractive errors. Sometimes, surgery on the extraocular muscles may be considered to improve eye alignment or reduce compensatory head postures. However, surgical outcomes can vary, and it may not fully restore normal eye movement due to the underlying muscular fibrosis. Regular follow-up with an ophthalmologist is essential to monitor vision and eye alignment. Early intervention for amblyopia, if present, is also crucial. Genetic counselling is recommended for individuals and families to understand the inheritance pattern and risks for future pregnancies.
Within the UK, care for CFEOM typically involves a multidisciplinary team. Access to these services is usually via tertiary specialist centres (often at Great Ormond Street Hospital or Moorfields Eye Hospital for paediatric and adult cases respectively) where ophthalmologists, orthoptists, and geneticists work together. NHS services provide comprehensive support for diagnosis, monitoring, and treatment.
UK care pathway
In the UK, individuals with suspected CFEOM will typically enter a care pathway that involves specialist paediatric or adult ophthalmology services, depending on age. Following an initial clinical assessment, a referral to a Clinical Genetics service is often made. These services can arrange for genomic testing via the NHS Genomic Medicine Service (GMS), using relevant R-codes from the National Genomic Test Directory. Genetic counsellors play a vital role in providing information and support to families regarding inheritance, testing options, and potential implications. This integrated approach ensures a comprehensive diagnosis and management plan.
Frequently asked questions
Can CFEOM be cured?
Currently, there is no cure for CFEOM as it is a developmental condition affecting eye muscles from birth. Management focuses on improving eye alignment and vision through treatments like corrective lenses, and sometimes surgery, but full restoration of eye movement is typically not possible.
Will CFEOM get worse over time?
CFEOM is a congenital condition, meaning it is present from birth. It is generally considered a fixed condition and does not typically worsen over time. The structural changes in the eye muscles are stable, though secondary issues like amblyopia can develop if not managed.
Is CFEOM inherited from my parents?
Yes, CFEOM is a genetic condition and can be inherited. The way it is passed down depends on the specific genetic change. It can be inherited in an autosomal dominant pattern (one copy of an altered gene) or an autosomal recessive pattern (two altered copies, one from each parent). Genetic counselling can help you understand your specific inheritance risk.
How is CFEOM diagnosed in the UK?
Diagnosis in the UK usually starts with a clinical examination by an ophthalmologist or paediatrician. If CFEOM is suspected, a referral to a Clinical Genetics service for genetic testing via the NHS Genomic Medicine Service will often follow. Imaging like an MRI may also be used to confirm findings.
What support is available for CFEOM in the UK?
In the UK, individuals with CFEOM can access support through multidisciplinary teams within specialist NHS centres. This includes ophthalmologists, orthoptists, and clinical geneticists. Genetic counselling is also available to help families understand the condition and its implications.
References
- Van Swol JM, Myers WK, Nguyen SA. Congenital Fibrosis of Extraocular Muscles: A Systematic Review and Meta-Analysis. Journal of binocular vision and ocular motility. 2023. PMID: 36780505
- Boricean ID, Bărar A. Understanding ocular torticollis in children. Oftalmologia (Bucharest, Romania : 1990). 2011. PMID: 21774381
- Yuksel Sukun E, Hamis Inal A, Ocak OB. Congenital Fibrosis of Extraocular Muscles: A Retrospective Study of 76 Patients. Cureus. 2024. PMID: 38975553
- Kerr K, McAneney H, Smyth L. Systematic review of differential methylation in rare ophthalmic diseases. BMJ open ophthalmology. 2019. PMID: 31799411
- Chen M, Huang R, Zhang Y. Phenotype, genotype, and management of congenital fibrosis of extraocular muscles type 1 in 16 Chinese families. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2023. PMID: 36138147
- Jia H, Ma Q, Liang Y. Clinical and genetic characteristics of Chinese patients with congenital cranial dysinnervation disorders. Orphanet journal of rare diseases. 2022. PMID: 36494820
- Sadiq MA, Ur Rehman M. Genetics of strabismus and lid diseases. Journal of pediatric genetics. 2014. PMID: 27625884
- Mravicic I, Lukacevic S, Biscevic A. A Treatment Approach in Congenital Fibrosis of Extraocular Muscles. Medical archives (Sarajevo, Bosnia and Herzegovina). 2023. PMID: 37260807