Overview

Identifying rare conditions involves more than meets the eye. Making a diagnosis for Cat Eye Syndrome requires both a thorough examination of physical signs and laboratory testing.

Diagnosis begins with noticing characteristic clinical features such as eye abnormalities and heart defects. To confirm the diagnosis, genetic tests are used to detect the extra genetic material responsible.

Read on to discover how a diagnosis is made for Cat Eye Syndrome, including the symptoms to look out for, the different types of genetic testing used, and why identifying the condition requires a thorough, comprehensive approach. 

What is cat eye syndrome?

The rare condition Cat Eye Syndrome (CES) is named after a notable feature present in some who have the condition, where a gap in the iris (coloboma) gives the eye a cat-eye-like appearance.¹ It is a genetic condition present from birth, affecting as few as one in 150,000 births.² 

Chromosomes are made up of DNA and hold the body’s genetic information. Those affected by CES usually have a partial extra copy of chromosome 22, leading to some of the genes on this chromosome having 4 copies instead of the usual 2 copies. It is this extra genetic material which leads to the features seen in CES.²

CES can affect various organs and systems in the body, such as the heart, eyes, and kidneys. Not all individuals with CES will exhibit the same symptoms and features, including the typical ‘cat eye’ appearance. The severity of symptoms and long-term health outcomes also vary.¹ Due to this great variability, a thorough and personalised approach to diagnosis and treatment is crucial. This article discusses the journey medical professionals take to diagnose CES. 

Common signs of cat eye syndrome 

Understanding and identifying the clinical features of CES is the first step towards making a diagnosis. The most well-known presentation of CES is a combination of the iris coloboma, a blocked or absent anal opening, and small pits and/or skin tags around the front of the ear.³  However, many individuals may not exhibit these features due to the great variety of features between those affected,^2, highlighting the importance of understanding the various possible signs one may present with. 

‘Cat eye’ appearance

A distinctive feature of CES, the coloboma of the iris, leads to a visually elongated pupil, causing the eyes to appear almost cat-like. This does not impact the individual’s vision; however, if deeper areas of the eye are involved, they may experience problems with their vision and even blindness. It should be highlighted that colobomas do not occur in all CES cases. 

Other eye conditions may also be present, such as one eye being unusually smaller than the other, crossed eyes, lack of an iris, or cataracts.⁴

Anal Irregularities 

The majority of people with CES will have a narrow or absent anal opening. They may also have a connection from their bowel to another body part (fistula), causing waste to flow through this passage instead.⁴ 

Ear irregularities 

Small pits and/or skin tags around the front of the outer ear is the most common sign observed in most cases of CES. The ears might have a lower position on the head, and can be abnormally shaped. The ear canal may, in some cases, be narrow, closed off, or absent, leading to partial hearing loss.⁴

Heart conditions 

Structural heart defects are present from birth in around half of those with CES. 

The most common example is total anomalous pulmonary venous return (TAPVR). This is where the pulmonary veins, responsible for carrying oxygenated blood from the lungs to the left side of the heart, incorrectly carry the blood into the right side, causing it to mix with deoxygenated blood. Individuals with TAPVR may exhibit features such as blue-toned skin pigmentation resulting from low oxygen levels in the blood, rapid breathing, and potential heart failure.

Tetralogy of Fallot (ToF) is another common condition, made up of four co-occurring defects: a ‘hole’ in the wall between the bottom chambers (ventricles) of the heart, partially blocked blood flow to the lungs, abnormal positioning of a major artery, and a thicker wall around the right ventricle.⁴

Kidney defects

Incomplete kidney development, having one less or one extra kidney, swelling, and cyst formation in the kidneys can occur in individuals affected by CES.⁴

Patient examination

Clinical examination of the individual can be carried out from birth to physically identify the signs of CES; some signs can also be examined before birth.⁴ Medical professionals will perform detailed checks on body areas which can be involved, to assess whether these are affected by the condition, allowing them to organise personalised care for the individual.¹

Examples of such examinations are:¹

• Inspecting skin tags around the front of the ear, or any abnormal ear cartilage
• Close examination of the eyes to determine the size and position of an iris coloboma 
• Scanning the heart to visualise its structure and how well it functions (echocardiogram), helping detect any defects 
• Kidney ultrasounds to scan for any defects, particularly relating to kidney presence/absence, size, shape, and blockages
• Foetal ultrasounds to detect potential heart/kidney defects in the foetus

Genetic testing 

Following a thorough clinical examination, a suspected CES diagnosis will be confirmed by genetic testing.

The go-to test for CES diagnosis is karyotyping.¹ This looks at an individual’s chromosomes, visualising their number and size to determine if the small extra piece of chromosome 22 is present. If this is observed, the individual can be diagnosed with CES. 

Another test, fluorescence in situ hybridisation (FISH), can confirm the presence of extra genetic material.¹ This uses fluorescent pieces of DNA (probes) which will bind to the specific section of chromosome 22 requiring detection. If the extra chromosome 22 material is present, fluorescent light will be seen. This confirms the individual has CES. 

Most people with CES do not have a family history of the condition, but in rare cases, it can be passed down from a parent. This can be determined by performing genetic testing of both parents. FISH testing with different DNA probes may be required to detect inherited CES. In these cases, genetic counselling is encouraged to guide families through what a diagnosis means for them and how the condition is passed down.¹

If CES is suspected in a foetus, a sample of foetal cells may be taken by withdrawing amniotic fluid (amniocentesis), or by taking tissue samples from the placenta (chorionic villus sampling). Karyotyping and FISH can then be carried out on these cells in the same way as usual.⁴

After diagnosis

There is no cure for CES; disease management focuses on helping relieve symptoms, and requires personalising treatments for each individual’s specific symptoms¹

• Surgical treatment is required to correct anal absence/narrowing and fistulas

• Heart defects may be treated with surgery, medication, or other therapies.⁴ Regular heart monitoring throughout the individual’s lifetime is recommended¹
• Regular monitoring of the individual’s eyes to detect further issues which can arise, such as cataracts. Some eye defects may require surgical intervention¹
• Monitoring kidney function and growth to check for any indications of kidney failure¹
• Hearing aids prescribed for hearing loss¹

Ongoing management must begin as early as possible to ensure those affected can achieve a higher quality of life from a young age.⁴

Summary

As a rare condition with great variability in its signs and effects on quality of life from one individual to another, CES may sometimes prove challenging to identify and diagnose. From the ears to the kidneys, the condition can affect various areas in the body and calls for a thorough approach at every stage, from initial examination to lifelong management. 

Initial examinations may begin before or after birth and allow medical professionals to assess whether clinical features of CES are present in an individual. Once the physical signs have been examined and any necessary physical testing has been carried out to form a suspected diagnosis, genetic testing is performed to confirm the diagnosis. This can involve visual assessment of the chromosomes to identify the presence of extra chromosome 22 material, or the use of DNA specific to the extra genetic material present in CES to determine whether it is present. 

Earlier diagnosis means earlier treatment, which can make all the difference for individuals’ quality of life with CES. Timely diagnosis ensures they can receive all the necessary treatments and manage symptoms more effectively, helping them live healthier, fuller lives.