What Is Cat Eye Syndrome?

Overview

Cat eye syndrome (CES), sometimes referred to as Schmid-Fraccaro syndrome, is a rare genetic condition that manifests as very specific physical and developmental traits. It develops as a result of a chromosomal defect in chromosome 22. A key sign of CES is the presence of coloboma, an abnormality in the eye that mimics a cat's vertical-slit pupil. The impact of this illness varies greatly, and symptoms can be minimal to severe.

Coloboma of the iris can impair vision. Preauricular tags or pits, heart malformations, kidney problems, and skeletal problems are other characteristics that may be present. Additionally, speech and motor deficits, along with intellectual and developmental difficulties, are frequently present.¹

Chromosomal analysis and clinical evaluation are frequently used to help choose the best course of action for treatment and management. Even though there is currently no cure for CES, there are management strategies available. The well-being of people with this illness must be improved by collaborative efforts from medical professionals, therapists, and educators. We are learning more about CES and its potential therapeutic approaches because of developments in genetic research.

Genetic background

Cat Eye Syndrome is primarily brought on by a chromosomal abnormality called a supernumerary bi-satellited marker chromosome 22. It occurs when a fragment of chromosome 22 is duplicated, adding an extra genetic component to the body. This abnormality develops during embryonic development. 

Excess genetic material can cause a variety of symptoms, such as developmental delays, coloboma (a distinctive eye anomaly), heart problems, and kidney anomalies. The distinctive characteristics of CES have been linked to mutations of various genes on chromosome 22, including the "SON" gene. These genes are essential for the control of healthy embryonic development, and their disruption may be a factor in the variety of clinical symptoms seen in affected individuals.² 

CES typically develops spontaneously as a result of a chromosomal defect that occurs during gamete creation or the early stages of embryonic development, rather than being passed down from parents. Given that the severity of symptoms can vary greatly, genetic counselling is essential for families who are at risk of developing CES. The medical, developmental, and educational needs of people with this syndrome must be managed, and early intervention is crucial.²

Clinical features

The main clinical signs of Cat Eye Syndrome include the following:

Coloboma 

This is the distinguishing sign of CES. It describes a gap or hole in the structures of one or both eyes. The anomaly is most frequently found in the retina or the iris, the pigmented portion of the eye. Different degrees of vision impairment can be caused by colobomas.

Anal atresia

Anal atresia is a congenital disorder in which the opening of the anus is either non-existent or partially closed, affecting a large number of people with CES.³

Preauricular tags or pits

Individuals with CES frequently have tiny preauricular skin tags or pits to the front of their external ears (the pinna).

Congenital heart defects

Some individuals with CES may have structural abnormalities in their hearts and blood vessels which formed during embryonic development. Congenital heart defects are present at birth.  

Renal (kidney) anomalies

Individuals with CES may also have severe kidney abnormalities, such as underdevelopment of the organs and in some cases, the complete absence of one kidney. 

Facial dysmorphism

Although facial features can vary greatly, patients with CES may have unique facial characteristics, such as small jaws, downward-slanted eyes, and hypertelorism (widely separated eyes).

Growth and developmental delays

People with CES may experience physical growth delays, as well as delays in the acquisition of speech, motor skills, and cognitive capacities.

Intellectual and developmental difficulties

Many people with CES have mild to moderate intellectual and developmental disabilities.

Cleft palate or cleft lip 

Cleft palate and cleft lip are congenital conditions where there is a split or opening in the upper lip or the roof of the mouth.

Hearing loss

In some circumstances, sensorineural hearing loss, a form of hearing loss that develops in the inner ear, may be present.⁴

Diagnosis of cat eye syndrome

Clinical evaluation

A complete physical examination is done to check for any signs of CES, including colobomas of the iris or retina, preauricular tags or pits, anal atresia, cardiac anomalies, facial dysmorphism, and developmental delays.

Genetic testing

• Karyotype analysis: This chromosomal examination can detect the existence of the particular chromosomal defect that is responsible for CES (known as supernumerary bi-satellited marker chromosome 22)
• Fluorescence In Situ Hybridization (FISH): FISH is a genetic testing method that can identify particular DNA sequences on chromosomes. It can be used to verify the existence of the supernumerary bi-satellited marker chromosome⁵
• Chromosomal Microarray Analysis (CMA): This high-resolution genetic testing technique can spot sub-microscopic chromosomal abnormalities, such as duplications, deletions, and other structural DNA changes. It may be able to pinpoint the precise genetic alterations connected to CES. 

Eye exam

Ophthalmologists can conduct a thorough eye exam, including an eye test on a dilated pupil, to determine whether colobomas or other eye abnormalities are present.

Imaging studies

• Cardiac evaluation: Cardiac imaging tests, such as echocardiography, may be carried out to assess the heart for structural abnormalities
• Imaging techniques, such as ultrasounds, can be used to examine the kidneys for any structural problems.

Developmental and cognitive evaluations

It's critical to perform developmental and cognitive evaluations to identify the severity of any intellectual and developmental disorders, as well as any delays in speech, motor, and cognitive development.³

The prognosis for cat eye syndrome 

Based on the severity of the accompanying characteristics, the prognosis for CES varies greatly. Milder forms can be managed medically and with supportive care, allowing patients to enjoy healthy lives. Medical concerns may be more challenging for people with more severe defects, such as cardiac or renal problems. Long-term outcomes can also be affected by intellectual and developmental problems.

Quality of life can be enhanced by early intervention and multidisciplinary treatment, including surgery for certain defects. Unless there is serious organ involvement, CES often does not have a significant impact on lifespan. Regular medical follow-up, developmental support, and genetic counselling are key to managing patients with CES.⁶

Current research 

The goal of current Cat Eye Syndrome (CES) research is to better understand the molecular processes behind the many clinical manifestations of the disorder, with a particular emphasis on the association between symptom presentation and the supernumerary bi-satellited marker chromosome 22. 

More accurate identification of the genetic variants underlying CES is now possible thanks to developments in genetic and genomic technologies. Researchers are also looking into how these genetic variations affect developmental pathways to identify possible treatment targets. 

The future directions in research involve the improvement of diagnostic standards and the investigation of personalised therapeutic strategies. Expanding patient registries and collaborative initiatives will also provide a greater understanding of the prevalence and variability of CES, improving clinical care and shedding light on associated genetic illnesses.⁷

Summary

Cat eye syndrome (CES) is a rare genetic illness with a distinctive range of clinical characteristics, the main one being coloboma of the eye. Clinical assessments, genetic tests, and imaging studies are all necessary for the diagnosis of CES. Our understanding of this complex condition is still being improved by advancements in genetic and genomic technologies. By encouraging these initiatives, we can better assist those who have CES and their families while also shedding light on more general genetic and developmental mechanisms.