Overview

Fryns syndrome is a rare autosomal recessive genetic condition caused by changes in the PIGN gene. Individuals with Fryns syndrome usually present with defects of the diaphragm, underdeveloped lungs, shortened fingertips and toes, and facial dysmorphia.¹ The defects can be diagnosed at birth or in utero. This article will provide a comprehensive overview of ocular abnormalities associated with Fryns syndrome, along with their diagnosis methodology and management strategies.    

Ocular abnormalities in Fryns syndrome

Around 15% of individuals with Fryns syndrome suffer with one or more ocular abnormalities that can lead to significant visual impairments and impact overall eye development.² The following section will detail each ocular abnormality and possible complications in relation to eye development, or eye conditions in the the anterior (front), or the posterior (back) parts of the eye.

Abnormal development of the eye and eye socket 

Hypertelorism

Hypertelorism is when the eyes are spaced farther apart than usual, with a wider gap between the inner and outer corners of the eyes.³ This is a typical characteristic noted with other facial characteristics in Fryns syndrome.¹

Microphthalmia and anophthalmia

Microphthalmia is defined as an abnormality where one or both eyes are unusually small, whereas anophthalmia is defined as the absence of one or both eyes. It has been noted that anophthalmia is considered rare in association with Fryns syndrome, whereas microphthalmia is more frequently recorded.^1,3   

Abnormalities of the anterior segment 

Cloudy cornea 

The cornea is the transparent, curved surface that covers the front of your eye. A classic characteristic in Fryns syndrome is a cloudy cornea. Cloudiness can occur in the centre or near the centre (parcentral) part of the cornea. In some cases, the cloudy cornea can be caused by irregularities in the outer corneal layer known as the bowman membrane or even microphthalmia.¹

Lens defects 

The lens is found behind the coloured part of the eye, and is transparent and flexible to help focus light on the retina to enable clear vision. In Fryns syndrome, the back of the lens can thicken with small pockets of empty space.^2,8 Infrequently, individuals can be diagnosed with cataracts in either one or both eyes.² 

Abnormalities of the posterior segment 

Hypoplastic optic nerve 

The optic nerve is a key part of the visual system and connects to the brain to send visual messages. Optic nerve hypoplasia is where the optic nerve is either small or underdeveloped leading to loss in vision. This condition is less commonly recorded in association with Fryns syndrome.^2,7,8   

Retinal dysplasia

The retina is a smooth layer at the back of the eye that is sensitive to light, it receives visual messages from the optic nerve and converts it into an image for an individual to see. In Fryns syndrome, individuals can infrequently be diagnosed with retinal dysplasia, where the retina is lumpy, folded and can develop new layers. This can impact an individual’s quality of vision. 

Eye-related complications

The ocular abnormalities discussed in the sections above can cause visual challenges for an individual. The following section will discuss impact on vision and related eye complications. 

Amblyopia 

Amblyopia occurs in childhood due to reduced vision in one or both eyes. Amblyopia can be caused by: structural ocular abnormalities such as cataracts, uncorrected glasses prescriptions or misalignment of the eyes (strabismus). 

Cornea related complications 

As described earlier, cloudy cornea is a sign of corneal dysfunction. This means it can be related to conditions such as; corneal infections, corneal dystrophies, corneal metabolic disorders, infantile glaucoma, or buphthalmos.^4,6 

Diagnosis and early detection

A prenatal ultrasound is used by clinicians to monitor a baby's health before birth. It can detect abnormalities like anophthalmia and microphthalmia as early as eighteen weeks into pregnancy.⁵ A foetal MRI is a way for clinicians to confirm possible abnormalities seen in a prenatal ultrasound.⁹ 

At birth, a clinical member of the ophthalmology team may use a slit-lamp or an ophthalmoscope, which is like a lighted microscope, to examine the front part of the eye, including the eyelids, cornea, iris, and lens. To examine the back of the eye, the clinician might use dilating drops to widen the pupil, allowing a clearer view of the optic nerve and retina.

Management and treatment options

While there is no cure for Fryns syndrome, treatment aims to manage the various malformations and symptoms associated with the condition. 

Surgery 

• Anophthalmia or microphthalmia: children with anophthalmia or microphthalmia may often require to enlarge their eye socket in order for an expanding device or prosthesis to be fit, or for the area to be filled in¹⁰ 
• Cataract: children with cataracts may require cataract surgery to help improve their visual potential¹²
• Infantile glaucoma/ buphthalmos: glaucoma and buphthalmos can cause blindness, and can require specialised surgical techniques to manage the condition. An individual with infantile glaucoma will have to continue to be monitored for the rest of their life due to the visual risks associated¹³  

Patching

Children with amblyopia can wear a patch over the eye with better vision for a few hours a day to help improve vision in the eye with reduced vision, by encouraging the brain to rely on the smaller eye with reduced vision.¹¹

Eye drops

• Corneal dystrophy: treatment for corneal dystrophy varies based on the type and severity of the condition. Often, eye drops like antibiotics, lubricating drops, or ointments can be used¹⁴
• Infantile glaucoma/buphthalmos: some individuals may require a combination of surgery as well as glaucoma eye drops to treat infantile glaucoma and buphthalmos¹³  

No treatment

Conditions such as retinal hypoplasia and optic nerve hypoplasia have no treatment options as the condition cannot be altered.^15,16 

Impact on quality of life

The outlook for eye-related issues in Fryns syndrome largely depends on the severity of the abnormalities.^1,2 Due to related ocular abnormalities and risk to an individual’s visual potential, an individual diagnosed with Fryns syndrome can require a team of specialists, including ophthalmologists to develop a personalised treatment plan. 

However, in cases with severe ocular malformations, alongside other critical issues diaphragm defects and underdeveloped lungs, the risk of early mortality remains high.⁸ For families impacted by Fryns syndrome, genetic counseling is advised to help them understand the inheritance patterns and assess the risks for future pregnancies.² 

Summary

Ocular abnormalities associated with Fryns syndrome can cause significant eye complications and even blindness. Treatment typically focuses on protecting the eyes, reducing discomfort, and enhancing an individual's quality of life. Early detection and specialised care are essential for managing the ocular abnormalities and eye complications. In cases with severe eye malformations, along with critical issues like diaphragm defects and underdeveloped lungs, the risk of early mortality is high.