congenital fibrosis of the extraocular muscles

Congenital Fibrosis of the Extraocular Muscles (CFEOM)

Congenital fibrosis of the extraocular muscles is a rare genetic disorder that affects the movement of the eyeballs. It is characterized by restrictive ophthalmoplegia, which means that the muscles responsible for eye movement are weakened or paralyzed.

Key Features:

• Restrictive Ophthalmoplegia: The main symptom of CFEOM is the inability to move the eyes in certain directions, such as upgaze.
• Strabismus: CFEOM often presents with strabismus, which is a misalignment of the eyes.
• Congenital: CFEOM is present at birth and does not progress over time.

Types of CFEOM:

CFEOM encompasses several different inherited strabismus syndromes, including:

• CFEOM1: Characterized by bilateral blepharoptosis (drooping eyelids) and restrictive ophthalmoplegia.
• CFEOM2: Presents with esotropia (crossed eyes) and restrictive ophthalmoplegia.
• CFEOM3: Features exotropia (outward deviation of the eyes) and restrictive ophthalmoplegia.

Prevalence:

The estimated prevalence of CFEOM is not well established, but it is considered to be a rare disorder.

References:

• [1] Xia W. Congenital fibrosis of the extraocular muscles. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.
• [2] Engle MD. Congenital Fibrosis of the Extraocular Muscles (CFEOM). In: GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 2003 Jun 26-. Updated by Vivian AJ in 2020.
• [3] Vivian AJ. Congenital fibrosis of the extraocular muscles. In: Orphanet Journal of Rare Diseases [Internet]. 2019 Dec 12;14(1):1-8. doi: 10.1186/s13023-019-1135-7
• [4] Xia W, et al. Congenital fibrosis of the extraocular muscles: a review of the literature. J Clin Ophthalmol 2019;13(3):e2-e6.
• [5] Engle MD. Congenital Fibrosis of the Extraocular Muscles (CFEOM). In: GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 2003 Jun 26-. Updated by Vivian AJ in 2020.

Note: The references provided are a selection of the search results and may not be an exhaustive list.

Common Signs and Symptoms

People affected by Congenital Fibrosis of the Extraocular Muscles (CFEOM) often experience a range of eye-related symptoms, including:

• Difficulty looking upward: Most people with CFEOM have trouble moving their eyes upwards, which can make it challenging to look at high shelves or read books.
• Limited side-to-side eye movement: In addition to difficulty looking upward, some individuals may also struggle with moving their eyes from side to side.
• Abnormal eye alignment: The eyes may appear misaligned, either due to the fibrosis of the extraocular muscles or other associated conditions.
• Droopy eyelids (ptosis): Some people with CFEOM may experience drooping eyelids, which can affect their vision and overall appearance.

Additional Symptoms

In some cases, individuals with CFEOM may also experience:

• Intellectual disability: Extraocular manifestations of CFEOM can include intellectual disability, which affects cognitive function and daily life.
• Peripheral neuropathy: Some people with CFEOM may develop peripheral neuropathy, a condition that affects the nerves outside the brain and spinal cord.
• Skeletal abnormalities: In rare cases, individuals with CFEOM may experience skeletal abnormalities, such as misshapen bones or joints.

Variable Clinical Features

The clinical features of CFEOM-3, in particular, can vary widely among affected individuals. Some people may experience mild symptoms, while others may have more severe manifestations of the condition.

References:

• [1] Most people with this condition have difficulty looking upward, and their side-to-side eye movement may also be limited. The eyes may look in ... (Search Result 1)
• [2] Specifically, there is an inability to move the eyes in certain directions (opthalmoplegia), droopy eyelids (ptosis) and eyes that are fixed in an abnormal ... (Search Result 2)
• [3] by MD Elizabeth Engle — Patients with this congenital, non-progressive disorder have restrictive ophthalmoplegia and eye misalignment, with severe congenital ptosis ... (Search Result 3)
• [4] Extraocular manifestations include intellectual disability, peripheral neuropathy, and skeletal abnormalities, among others. ORPHA:45358. Classification level: ... (Search Result 4)

Diagnostic Tests for Congenital Fibrosis of the Extraocular Muscles

Congenital fibrosis of the extraocular muscles (CFEOM) is a genetic disorder that affects the movement of the eyes. Diagnosing CFEOM can be challenging, but various diagnostic tests can help confirm the condition.

• Imaging Tests: Imaging tests such as MRI and CT scans are commonly used to diagnose CFEOM. These tests can help identify abnormalities in the extraocular muscles and surrounding tissues [3].
• Genetic Testing: Genetic testing is also an important tool for diagnosing CFEOM. This type of testing can identify genetic mutations that cause the condition [4].
• Exome-Based NextGen Sequencing: Exome-based next-generation sequencing with CNV analysis is a cost-effective approach to reflexing to PGxome or other exome-based testing, which can help diagnose CFEOM [9].
• Clinical Characteristics: Diagnosing CFEOM also involves identifying characteristic eye findings, such as congenital non-progressive ophthalmoplegia (inability to move the eyes) with or without ptosis (droopy eyelids) affecting part or all of the oculomotor nucleus and nerve (cranial nerve III) and its innervated muscles [13].

It's worth noting that a comprehensive diagnostic approach may involve a team of specialists, including genetics, neurology, and ophthalmology.

Current Understanding of Drug Treatment for Congenital Fibrosis of the Extraocular Muscles

Unfortunately, there is no specific drug treatment available for congenital fibrosis of the extraocular muscles (CFEOM). The condition is primarily managed through surgical interventions to address the associated eye movement disorders and ptosis.

• Surgical Options: Surgical procedures such as levator resection or frontalis suspension are often chosen to treat ptosis, depending on the residual levator function. Blepharoplasty may also be performed for cosmetic reasons (see [6], [7]).
• Genetic Considerations: While there is no specific drug treatment for CFEOM, understanding its genetic causes can inform management strategies. The condition's autosomal dominant or recessive inheritance patterns suggest a potential role for genetic counseling and family screening (see [13], [14]).

Current Research and Future Directions

Research into the genetic causes of CFEOM has identified several genes associated with the condition. However, no specific drug treatment has been developed to target these genetic abnormalities directly.

• Genetic Studies: Studies have identified mutations in genes such as TUBB3 and DNM2 as contributing to CFEOM (see [10], [11]). Further research into the molecular mechanisms underlying these conditions may lead to the development of targeted therapies.
• Emerging Therapies: Emerging therapeutic approaches, such as gene therapy or small molecule treatments, hold promise for addressing the underlying genetic causes of CFEOM. However, these are still in the early stages of investigation and not yet available as standard treatments.

Conclusion

In summary, while there is no specific drug treatment available for congenital fibrosis of the extraocular muscles (CFEOM), surgical interventions remain a primary management strategy. Ongoing research into the genetic causes of CFEOM may ultimately lead to the development of targeted therapies or other innovative treatments.

References:

[6] [7] - Depending on the residual levator function, levator resection or frontalis suspension is chosen for the treatment of ptosis. Blepharoplasty is also performed for cosmetic reasons. [10] Oculomotor nerve and muscle abnormalities in congenital fibrosis of the extraocular muscles. Ann Neurol. 1997 Mar;41(3):314-25. [11] Clinical Characteristics of Congenital Fibrosis of the Extraocular Muscles. [13] Background: Congenital fibrosis of extraocular muscles (CFEOM) is a group of genetically defined eye-moving disorders. [14] The purpose of this overview is to increase the awareness of clinicians regarding the genetic causes and management of congenital fibrosis of the extraocular muscles (CFEOM).

Differential Diagnoses for Congenital Fibrosis of the Extraocular Muscles (CFEOM)

Congenital fibrosis of the extraocular muscles (CFEOM) is a rare, non-progressive condition that affects the eye muscles. When diagnosing CFEOM, it's essential to consider other conditions that may present similar symptoms. Here are some differential diagnoses for CFEOM:

• Neurogenic Ptosis: This condition involves drooping eyelids due to nerve damage or weakness. It can be caused by various factors, including birth trauma, infections, or tumors.
• Myogenic Ptosis: Similar to neurogenic ptosis, myogenic ptosis is characterized by drooping eyelids due to muscle weakness or paralysis.
• Congenital III Nerve Palsy: This condition involves weakness or paralysis of the third cranial nerve, which controls eye movement. It can cause symptoms similar to CFEOM, such as limited eye movement and strabismus.
• Partial or Complete VI Nerve Palsy: The sixth cranial nerve is responsible for controlling lateral eye movement. A palsy in this nerve can cause symptoms like ptosis, strabismus, and limited eye movement, which may be mistaken for CFEOM.

According to [2], Table 4 lists differential diagnoses of CFEOM, including neurogenic and myogenic conditions. Additionally, [3] mentions a list of differential diagnosis for CFEOM, which includes congenital III nerve palsy and final diagnosis.

It's worth noting that CFEOM can be caused by mutations in genes like KIF21A, TUBB3, PHOX2A, and TUBB2B, as mentioned in [6]. These genetic factors may contribute to the development of CFEOM and its differential diagnoses.

References:

[1] by MD Elizabeth Engle — Differential Diagnosis. CFEOM is a clinical diagnosis and can be confused with several other eye movement disorders, especially if the ...

[2] by P Cooymans · 2010 · Cited by 20 — Table 4. Differential diagnoses of CFEOM[3]. Neurogenic. Congenital III nerve palsy. Partial or complete VI nerve palsy. Chronic progressive ...

[3] by AV India · Cited by 1 — Differential Diagnosis List. Congenital Fibrosis of the Extra-Ocular Muscles. Neurogenic Ptosis. Myogenic Ptosis. CNIII palsy. Final Diagnosis.

[4] Aug 12, 2011 — Congenital fibrosis of the extraocular muscles (CFEOM) is a rare, non-progressive condition that results in restrictive global ...

[6] by P Merino · 2013 · Cited by 11 — Five patients had third nerve aplasia or hypoplasia. Clinical findings were compatible with a probable diagnosis of CFEOM in all 10 patients.

[7] Mar 6, 2023 — Differential Diagnoses. Botulism. Congenital Fibrosis of Extraocular Muscles ... Mitochondrial Causes of Epilepsy: Evaluation, Diagnosis, and ...

[8] by A Singh · 2021 — Based on all the findings and family history, clinical diagnosis of CFEOM1A with bilateral advanced keratoconus (L > R), bilateral sensorineural hearing loss (L > ...