Overview

Cri Du Chat Syndrome, literally ‘crying cat syndrome’ can cause many health issues. It is caused due to a genetic abnormality, specifically, a deletion at the end of the short-arm of chromosome 5.¹ It can exhibit in many ways, with infants often crying distinctively like a cat, thus the name ‘Cri du Chat’. Facial defects also contribute to Cri Du Chat syndrome, along with issues such as underdevelopment of the brain which can cause physical and mental development issues, such as motor function and control.² This article will focus particularly on the visual issues caused by this chromosomal abnormality syndrome.

Incidence

Cri Du Chat syndrome occurs more commonly in females compared to males, with females affected almost 1.25 times more than males.⁸ This condition is present in approximately 1 in 15,000-50,000 live births, and the specific abnormalities caused by the deletion on chromosome 5 in between p5.12 and p15.13 determine the extent of the disability caused, with some children unable to survive long after birth.⁸

Visual structures affected by Cri Du Chat

Ocular Hypertelorism

One classic feature of Cri Du Chat syndrome is ocular hypertelorism which is observed at birth. This is when the eyes are set wide apart on the face, measured by a greater-than-average distance between the pupils. This is due to the eye sockets being set further apart in the skull.³ Extra bone fills in the space between the eye sockets to support the eyeballs, but visual issues are not caused by this factor alone. Though not entirely understood, this is caused near the end of the first trimester due to a complication which results in the prevention of the orbital sockets migrating towards the midline of the foetus’ face. This could be because of defects with the nasal capsule, such as freezing of the naso-fronto-orbito ethmoid complex, or its early ossification which could both cause this ocular hypertelorism.³ Since the 1960s complex surgery involving changes both inside and outside the skull can correct this without compromising vision, though this is largely done for aesthetic purposes as ocular hypertelorism in itself does not cause visual problems.³

Telecanthus

Telecanthus is a congenital condition where there is an increased distance between the two eyelids.⁴ This understandably can result when ocular hypertelorism is present as an increased distance between eyeballs will evidently lead to an increased distance between eyelids. In other illnesses, telecanthus can be present without ocular hypertelorism, in which case a fairly straightforward surgery can correct the issue. 

Epicanthal folds

Epicanthal folds are vertical eyelids that cover the inner corner of your eyes. These don’t normally affect vision and can be present in other congenital abnormalities too. 

Antimongoloid palpebral fissures

The palpebra are the top and bottom eyelids on one’s face. Palpebral fissures refer to the space between the two eyelids, which can naturally vary from person to person. Normally, the upper eyelid covers part of the superior portion of the eyeball, whereas the lower eyelid (palpebra) covers part of the inferior part of the eyeball and lies approximately within 1mm of the lower edge of the iris.¹¹ An antimongoloid slant is said to exist when the outer edges of the eye sit lower than the inner corner of the eye, thus making the eyes slant upwards towards the centre of the face.¹² Such is the case in many Cri Du Chat cases, although the degree of slant may vary between patients. 

Exotropia

Exotropia is when one or both eyes deviate from the central line of vision, meaning that one eye will be pointing outwards at an odd angle when you are looking straight ahead. This is normally observed as an angle deviation of more than 20^O in Cri Du Chat patients, with patients often seeing less compared to healthy children.^5,6 Due to angular defects, there is often greater overlap in the area which can be seen from both eyes, called binocular vision.⁵ After one year of age, overactivity of the external oblique muscles which control where the eye turns can occur, as well as one eye vertically as the other eye focuses on a target.⁵

Optic nerve atrophy/ hypoplasia

Over time there has been some debate as to whether the optic nerve fibres begin to slowly die during Cri Du Chat, or whether not enough fibres are continuously produced in the first place.⁷ Previously reported cases of Cri Du Chat have reported cases of both of these conditions, although it is debatable which of these conditions truly existed in these patients, especially as the condition develops in utero between the first and second trimester.^1,8 It is also possible for hypoplasia and atrophy to both occur within the same fibres.⁷ Regardless, scans show a reduction in optic nerve fibres, which can lead to less photoreceptor information being carried to the brain, and permanently reduced vision as a result. The optic disc (the small disc at the back of the eyeball which connects to the optic nerve) is often grey and pale too, and at most half the size it normally is.¹⁶ It therefore is also unable to transmit as much information to the brain from the photoreceptors, which can lead to the visual field becoming dimmer and less focussed.                                                

Tortuosity of the retinal vasculature

The retina is specialised tissue within the eye that contains photoreceptors that allow us to detect light and make sense of the world around us. It is quite sensitive and has a specific blood supply as well as supportive pigment epithelium that both enable it to work optimally.⁹ The retinal vessels are normally smooth and straight, or slightly curved, which allows blood to pass quickly and easily through the vessels. However, in the Cri Du Chat, the retinal vessels are more tortuous with many branches that take turns throughout the retina.¹ A study with 48 tasks has suggested that greater tortuosity in the retinal framework has been associated with greater behavioural issues within young children.¹⁰ This may be due to decreased attention spans as vision issues may occur. As the retina forms from the same embryonic structures as the brain, and thus has many similarities to it, it is entirely possible that earlier dysfunctions in brain development also translate to the retina and its vessels.¹⁰ However, the mechanisms through which this occurs are not yet known. Animal studies have demonstrated that anaemia during pregnancy or decreased perfusion both led to more tortuous vasculature within the foetus, suggesting that this may possibly also play a part in the decreased cognitive abilities seen in Cri Du Chat patients with tortuous retinal vasculature.¹⁰

Corpus callosum abnormalities

The corpus callosum is a structure which acts as a bridge between the left and right halves of the brain. In Cri Du Chat syndrome it may not be fully formed or partially atrophied, which can result in many issues including vision defects.¹³ This partial degeneration/ underdevelopment of the corpus callosum was randomly studied in 19 children over 10 years.¹⁴  Although 38% had very mild vision loss, the other suffered greater visual impairment. Blurred vision occurrence was possible in 62% of patients due to refractive issues where the light entering the eye would not focus directly on the retina. Nystagmus was also observed in 15% of patients with partial corpus callosum underdevelopment, which is rapid uncontrolled erratic movements of the eye in different directions.¹⁵ This of course can make it very difficult to focus with the affected eye(s), thus causing visual impairment. In rare cases, (8%), microphthalmia occurred as a result of abnormal corpus callosum development.¹⁴ This is when one or both of the eyes are unusually small. This can cause severe visual issues, though it is possible to have fairly good visual focus if the optic nerve is not involved in the deformity.¹⁷ In many cases the microphthalmia can result in a smaller, opaque cornea which doesn’t let a lot of light enter the eye, the pupil may not sit at the centre of the iris, the eye lens may be displaced from its correct position within the eyeball, the iris may be partially or completely absent, cataracts could occur, the retina may be malformed or the foetal blood vessels may still be present in the eye along with the child’s, causing the eye to reflect silver light instead of red.^17,18 All or some of these conditions may occur due to the corpus callosum defects caused by Cri Du Chat, although this would depend on what part of the corpus callosum is specifically affected and which mutations caused the disease.

Summary

Cri Du Chat syndrome can cause a variety of health issues, and lead to a variety of vision defects such as poor kinetic/ spacial awareness, blurred vision and reduced vision.¹⁹ Many defects of the eye may be observed such as a downward slant of the eyes, small eyes, small or absent irises, or an out-turned eye. The defects seen are often coupled with cognitive impairment, and although the pathophysiology behind the specific deformities seen is not yet completely understood, brain development abnormalities which lead to cognitive impairment may also contribute to the vision defects seen as the eye and brain are closely related embryologically. The abnormalities seen would depend on the length of the genetic information deleted on chromosome 5 which can vary between patients.