Introduction

Human eyes are distinct looking, characterised by a circular iris which appears in different colours and a round pupil in the middle. Being an important and essential part of the body, any damage to the eyes can have a dramatic effect on our vision and ability to perform daily tasks. This article will discuss Cat Eye Syndrome, what it is, and its causes.

What is Cat Eye syndrome

Cat Eye Syndrome (CES), also known as Schmid-Fraccaro syndrome, is an uncommon disorder of the eye that affects the pupils. It is a genetic disorder characterised by an elongated, almost oval shape of the pupils, like the pupils of a cat. This mutation is caused by an extra copy of chromosome 22, which is the second smallest chromosome in the body and makes up around 2% of the total DNA present. Chromosome 22 has a short arm, which is called p, and a long arm called q, categorising it as an acrocentric chromosome.

Diagnosis is extremely important in CES. Early diagnosis can be crucial in administering the correct treatment and improving patient care and quality of life. Certain genetic and clinical features overlap with CES, such as DiGeorge syndrome and Oculo-Auriculo-Vertebral (OAV) spectrum, which makes differential diagnosis difficult.¹

Clinical features

There are several key characteristic signs present in individuals with cat eye syndrome and three of them are very distinct and visual. The main features of CES are:

• Iris coloboma: which is the appearance of a cat’s eye, which is caused by an elongated pupil
• Anal atresia: which is when a newborn child does not have a normal anal opening. This could be mild (a membrane covering the area) or severe (the anus is absent)
• Preauricular skin tags or pits: with tags being extra bits of skin stuck to the earlobe and pits being small holes in front of the ear

Although most people with CES may have all the main features, it is not guaranteed in all cases. Some people may have other symptoms, such as:

• Cardiac defects
• Anomalies in the kindneys and urinary system with varying degrees of severity
• Skeletal abnormalities
• Otolaryngological manifestations (ENT symptoms)

It might occasionally be more challenging to identify CES in certain people due to the variations in symptoms.^1,2

Diagnostic tools and methods

There are several methods to diagnose CES and 3 of these methods are:

Family history

Most cases of CES are sporadic, however, it can be hereditary if even one of the parents has the genetic mutation but shows no symptoms. Therefore, a family history could provide useful information on whether or not the individual had inherited the condition from a parent.¹

Physical assessment

A full physical examination is necessary since the findings are diverse and typically involve many organ systems. These clinical findings of CES can be classified systematically based on the organ systems involved. 

Genetic testing

Genetic testing of chromosome 22 to identify a mutation would be definitive proof. Karyotyping is usually adequate to diagnose CES, whether prenatally or postnatally. However, fluorescence in situ hybridisation (FISH) is another type of genetic testing that can be performed to identify and diagnose CET. Unlike karyotyping, which provides an overview of all 46 chromosomes, FISH is a faster technique that targets smaller and more specific regions of chromosomes through the use of fluorescent probes. In hereditary cases, genetic counselling is indicated to assist families in determining the likelihood of recurrence and understanding the implications. ³

Similar conditions

There are a number of conditions that have similarities to CES in either the genetic location or the fact that similar organs are affected. A few of these conditions include: 

• DiGeorge syndrome (DGS): both of these conditions affect chromosome 22. However, unlike CES, DiGeorge syndrome is a deletion in the chromosome, causing a loss of genetic material. Although iris coloboma is only visible in CES and not DGS, heart abnormalities, renal malfunctions and kidney issues are several similarities between the two conditions 
• CHARGE syndrome: the acronym stands for some of the common symptoms, coloboma, heart defects, atresia, growth retardation, genital abnormalities and ear abnormalities. Some of the symptoms are common with CES but not necessarily pits and tags. The difference arises mostly in the blockage of the nasal passage or choanae that is present in CHARGE
• Oculo-Auriculo-Vertebral (OAV) or Goldenhar syndrome: is an uncommon condition that causes a fault in the development of one or both sides of the face, with the ears, eyes and jaw being affected the most. It is a very rare condition with an unknown cause, but it can cause coloboma issues (albeit not the same way as CES) and also possibly issues with the ears, which can be similar to CES. However, CES is a genetic chromosome disorder, while OAV is part of a spectrum, which can make differentiating them easy via chromosome testing

Although many of these disorders may share visual similarities with CES, the most accurate method of diagnosis is through genetic testing of chromosome 22, which provides the most reliable result.^1,4,5

Summary

Human eyes are unique, featuring a circular iris and a round pupil, and any damage can significantly impact vision. Cat Eye Syndrome (CES), a rare eye disorder linked to a genetic mutation that affects the shape of the pupils, making them appear elongated like a cat's. The disorder results from an extra copy of chromosome 22, which represents about 2% of human DNA. Early diagnosis of CES is vital for proper treatment and care, though distinguishing it from related conditions such as DiGeorge syndrome and Oculo-Auriculo-Vertebral spectrum can be challenging. Key features of CES include iris coloboma, which results in the cat-eye appearance, anal atresia where a newborn has no normal anal opening, and preauricular skin tags or pits. While many individuals with CES exhibit all these main characteristics, others may show different symptoms like heart defects or urinary system anomalies, making identification sometimes difficult.

Diagnosis of CES involves several methods. A family history can help determine if the condition is hereditary, especially if a parent carries the genetic mutation without symptoms. A thorough physical examination is also necessary since CES may impact multiple organ systems. Genetic testing is crucial, with karyotyping providing an overview of chromosomes and fluorescence in situ hybridisation (FISH) offering a faster and more specific analysis. Genetic counseling is beneficial for families to understand the risks and implications of the condition. CES shares similarities with conditions like DiGeorge syndrome, which also affects chromosome 22 but involves a deletion rather than a duplication. CHARGE syndrome shares some symptoms but has unique characteristics, while Oculo-Auriculo-Vertebral syndrome impacts facial development. Genetic testing of chromosome 22 remains the most reliable way to diagnose CES and differentiate it from other disorders with overlapping features.