Marfan Syndrome And Ocular Manifestations

Overview

When it comes to diseases associated with defective connective tissues, a multi-system effect is usually the result, with devastating consequences if not managed. This is because connective tissues are found in virtually all areas of the body including your eyes. 

Marfan syndrome affects several parts of the body; hence, it is a very complicated condition. It also affects people in different ways; some have all the features, while others have only a few. Some have severe problems, especially with the cardiovascular system; others don’t feel it quite so vigorously. As this condition can be potentially life-threatening, this article is aimed at helping you understand how Marfan syndrome can manifest in the eyes.

What is marfan syndrome?

Marfan syndrome is a systemic connective tissue disorder that is inherited in an autosomal dominant pattern.¹ This means that even if one of your two copies of the gene is normal, a single mutated copy of the gene is enough to still cause the disease. 

The connective tissue is a vital structural component in the body. It serves as a kind of glue that holds tissues and organs together. It also promotes normal growth and development. Since connective tissues are found throughout the body, different organs can be affected by the disorder. These include the heart, blood vessels, eyes, lungs, bones, joints, and skin. Some of these defects can lead to severe complications and may be life-threatening. 

The estimated prevalence of Marfan syndrome is 1 in 10,000 to 20,000 individuals.² It has no gender, racial, or ethnic preference. It is also referred to as arachnodactyly because this is one of the signs of Marfan’s syndrome. Arachnodactyly is characterised by unusually long slender fingers and toes.³ Other signs common in Marfan Syndrome include tall stature, scoliosis, or high-arched palates. People with this disorder may also have heart murmurs and vision issues, such as extreme myopia.¹

What causes marfan syndrome? 

Marfan syndrome is caused by a mutation in the gene that codes for a glycoprotein called fibrillin-1. Fibrillin-1 is an extracellular protein that forms a major component of microfibrils (i.e. rope-like structures that provide tissue integrity and form connective tissues). This protein is essential for normal fibrillogenesis (normal development of fibrils).⁴

This fibrillin-1 mutation has two major consequences; an increase in a protein called transforming growth factor beta (TGF-ß) and disruption in the formation of microfibrils. This results in fibrillin protein abnormalities and subsequent weakening of the connective tissues.⁵ Normally, fibrillin regulates tissue growth and inhibits the activity of TGF-ß, which stimulates tissue growth. 

In other words,  less fibrillin (due to mutation) = more tissue growth. 

The increase in TGF-ß causes problems in tissues throughout the body, which create the features associated with Marfan syndrome (long and slender fingers and toes). 

According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases, it is possible to inherit the mutation from a parent who has the disorder. This is the case in about three out of four people with Marfan syndrome. There can also be spontaneous mutation, meaning that the person is the first in their family to have Marfan syndrome. People with Marfan syndrome have a 50% chance of passing the mutation each time they have a child. 

How marfan syndrome manifests in the eyes

Marfan Syndrome can affect the eyes in many ways. This is because fibrillin-1 is located in different parts of the eyes such as the conjunctiva, iris, ciliary body, corneal stroma, optic nerve, lens, choroid, and vitreous. These fibrillin-rich microfibrils regulate development and confer strength and elasticity to connective tissues. Fibrillin that is present in the equatorial region of the lens capsule allows anchorage of the zonular fibres. ⁶

Marfan syndrome manifests in the eyes in the following forms:

Dislocated lens (Ectopia lentis) 

This is one of the major diagnostic criteria for Marfan syndrome. This means the lens, located at the front of the eyes, has slipped out of place. It occurs because the tissue (called zonules) that holds the lens in place becomes weak. It can slip a little or completely out of place. Dislocated lenses can cause problems with vision and astigmatism, which can also lead to distortion that may or may not be corrected with glasses. ⁷

Fig 1: Lens dislocation in a patient with Marfan syndrome.¹²

Retinal detachment

This is the detachment or separation of the light-sensitive membrane in the back of the eye (i.e. the retina) from its supporting layers. Several factors can predispose a patient with Marfan syndrome to develop retinal detachment. The majority of patients with retinal detachment usually have ectopia lentis. The instability of the dislocated lenses exerts a pulling force on the vitreous base. This can lead to small tears or holes in the retinal periphery. Patients may develop aphakia-like retinal detachment.⁸

Glaucoma 

This occurs due to optic nerve damage from elevated intraocular pressure. This condition is more prevalent in people with Marfan syndrome than in people who don’t have this disorder.

Pre-senile cataract 

Cataracts are common in older people who do not have Marfan syndrome. However, people with Marfan syndrome can develop cataracts even before 40 years of age. 

Fig 2: Cataract vs glaucoma manifestation in Marfan syndrome

Severe myopia

This is also known as nearsightedness. It occurs because the focal point of the images lands in front of the retina, instead of on the retina.
Amblyopia

This is often referred to as lazy eye. It occurs when one eye doesn’t develop normal vision from childhood. 

Fig 3: Amblyopia or lazy eye 

Strabismus

This is commonly known as crossed eyes and is a frequent feature in Marfan syndrome. If uncorrected in children, it can result in amblyopia. It is present in 19% to 45% of individuals with Marfan syndrome. ⁹

Fig 4: Strabismus or crossed eyes

Patients with Marfan syndrome may also have flat and thin corneas; megalocornea may also be present.¹⁰ Hypoplastic iris or ciliary muscle can also be seen. 

Other body systems affected by marfan syndrome 

Making reproductive decisions with marfan syndrome

When one parent has Marfan syndrome, each pregnancy has a 50% chance of inheriting the mutation (i.e. autosomal dominance).¹³ Also, in some instances where both parents have Marfan syndrome, genetic counselling is required to inform the parents of the consequences of having children with this condition as well as other available options.¹³ This is because of the severe complications that the child could face, which might include neonatal death.¹³

Thus, the following options are available for consideration:

• Prenatal diagnosis via amniocentesis or chorionic villus sampling 
• Preimplantation genetic diagnosis¹³
• Gamete (sperm or egg) donation
• Adoption¹³

Summary 

• Marfan syndrome is usually thought of as a condition of loose ligaments, which can manifest in the eyes, heart, lungs, bones, and joints with debilitating effects. 
• Ocular and cardiovascular involvement pose the most severe threats associated with this condition. 
• Clinical diagnosis and management is a collaborative effort by different health professionals, as it is a multisystem disorder with varying degrees of severity. 
• Genetic counselling is also paramount to advise parents on the genetic implications of having a child or children with Marfan syndrome. 

FAQs

At what age does Marfan syndrome typically appear? 

The physical features are sometimes present in infancy but more often show up later in childhood or adolescence.

What is the greatest risk for someone who has Marfan syndrome?

The greatest risks associated with this condition include those of the cardiovascular system, particularly the heart valves and aorta.

What treatment options are available for Marfan syndrome? 

Marfan syndrome has no cure. However, management is aimed at limiting cardiovascular complications. This is achieved by reducing stress and workload placed on the cardiovascular system as well as other lifestyle modifications.