Introduction 

Cat eye syndrome (CES), otherwise known as Schmid-Fraccaro syndrome, is a rare genetic disorder that affects almost 1 in 150,000 births.¹ It is caused by the duplication or triplication (in more severe cases) of chromosome 22 in humans, which leads to abnormal fetal development and an array of variable physical and behavioural characteristics. CES can create a neuropsychomotor delay in the affected babies.²  This means that CES affects the child's development in areas like movement, coordination and cognitive skills. 

The disease has three clinical features: a distinct ‘cat-eye’ shape in the vertical coloboma of the iris, meaning a section of the tissue within the iris is missing; malformations in the ears (preauricular tags); and anal atresia (an abnormal obstruction of the anus). There may be involvement of other organs and systems as well, including kidney and heart defects.^1,2 

However, these associated characteristics of CES vary greatly in severity and presentation depending on each person. As a result, symptom manifestation within this condition can differ significantly. Research indicates that at least one of the clinical signs, in particular, the iris coloboma, is missed on the first clinical evaluation.³

There are different neurological and behavioural consequences for a person living with CES, which can impact a person’s quality of life as well as their mental health. In particular, colobomas can cause a person to have worsened vision or increase their risk factors for anxiety regarding their diagnosis. Additionally, some people with CES are diagnosed with congenital heart disease or scoliosis, which may impact their ability to exercise normally. A strong support system can help manage the added pressures of living with CES. Relevant treatments will be suggested by your doctor to pursue the best course of action. 

Neurological features

CES affects the central nervous system (the brain and spinal cord), which can have an impact on day-to-day life in comparison to someone without the condition. However, these neurological differences vary significantly between individuals, which is why it is important to be comprehensively screened at a young age and monitored for the condition if there is a family history of CES. 

Abnormalities found in those with CES affect the structure and function of the brain. For example, cerebral hypoplasia describes a brain difference where the cerebellum appears smaller in size in people with CES. Additionally, cerebellar atrophy, also known as cerebellar degeneration, can occur, whereby the cerebellar tissue shrinks.² Other cases have seen changes in the size of the brain as well as the pituitary glands, despite minimal impacts on hormone levels in children with CES.⁴ Therefore, further research is needed to better understand the mechanisms of this condition and how it affects people’s brain health. 

Developmental delay

For those with CES, delays in neuropsychomotor development have been reported, affecting intellectual function, motor skills, and the child’s overall developmental progress. Such delays could lead to cognitive and social difficulties later on in a child’s life. Therefore, early diagnosis is important to ensure timely interventions and proper childhood development.⁵ 

Some children have been seen to have hypotonia, where muscle tone and function are weakened due to a constant resistance to stretch. This can have knock-on effects on the motor development of the child, such as being able to latch on during breastfeeding or even further on in their motor skills, like trouble sitting or walking.⁶

Some people may be diagnosed with CES as a result of severe neuropsychomotor delays, which is an important indicator for clinical assessment. However, extremely severe cases have also been attributed to other genetic factors, not just chromosome 22 abnormalities associated with CES, suggesting a potential overlap or misdiagnosis in symptoms.³ 

Behavioural features

As a consequence of CES and its impact on the nervous system of a child, they may experience different behavioural patterns, and some children may show delays in key milestones such as sitting upright or walking as a result of neurological impairment. This is a direct result of the congenital abnormalities from their birth with CES. For example, a child’s posture may not be properly developed until later on in life, and they may have trouble supporting their head.⁶ Some children have also been seen to have difficulties with speech and language skills as they grow, where there is a need for a language therapist to help them learn better ways to communicate.⁴ 

Neurodiversity with cat eye syndrome

Furthermore, a small number of patients have been shown to develop autism spectrum disorders and ADHD due to attention deficits and hyperactivity. This neurodiversity may be attributed to the changes in neurological features. There have also been a few cases of anxiety disorders as a result of CES. However, it is important to note that these may not be present in all cases and were only shown in a few cases of children with CES.⁶ 

Clinical assessment and management

Assessment tools

Usually, CES is assessed at birth, using cytogenetic testing or other genomic screening tests used for chromosomal analysis. However, individuals with mild symptoms may not be identified immediately, highlighting the importance of genetic screening when there is a known family history of CES.

Not all patients with CES will present iris coloboma, which makes clinical diagnosis harder. Therefore, it is important to focus on genetic screenings as well as keeping an eye on the heart and other important symptoms of CES.¹ Psychological assessment may also need to be prioritised, due to the reports of anxiety and neurodiverse conditions. 

Given the wide variability in symptom presentation and the challenges a child may face, a holistic, multidisciplinary approach to clinical assessment is essential, encompassing physical, neurological, and behavioural evaluations.

Interventions and treatments

As with most disorders, the management of CES depends on the organs affected. If a person’s vision is primarily affected, then ophthalmologists may need to get involved early to prevent further visual impairment. If a person’s heart is affected with a defect such as a murmur, cardiologists must strategise a monitoring plan and decide if surgical treatment is required.¹

Early interventions and treatments for the heart, kidneys, biliary and digestive systems may prevent future complications. However, the intervention is dependent on the severity of CES, and an integrated approach to treating CES seems to prove the best for improving quality of life.³ Furthermore, it is important to check all the areas that CES may affect, and understand the level of severity of the condition. In cases of CES associated with Duane syndrome, continual monitoring may be suggested to monitor and prevent ocular motor dysfunction from developing further in the child’s life.³ 

In order to treat the behavioural as well as physiological symptoms of CES, a dedicated team of doctors, including psychologists, would work to help ensure a better quality of life for the patient. Children with language and speech difficulties may also be referred to a speech therapist to improve their communication skills and develop strategies to manage their condition.⁴ Moreover, a multidisciplinary approach to treatment is required for the effective long-term management of CES. 

Summary

Cat eye syndrome, which is also referred to as Schmid-Fraccaro Syndrome, is a rare genetic condition with varying clinical presentations. It primarily affects children between the ages of 0-12 months, affecting almost 1 in 150,000.¹ It arises from genetic mutations in chromosome 22 and is more likely to occur if there is a family history. 

CES has three main clinical presentations: a missing tissue in the iris known as a vertical coloboma, preauricular tags (affecting the ears), and anal or rectal malformations. However, symptoms may also include complications in heart function, urinary system and neurological development. Some cases have also been associated with Duane syndrome, which affects the movement of the eye. CES can impact a patient by affecting brain development and, in some extreme cases, cause seizures or hypotonia. 

Behaviourally, children may not be able to reach major milestones until later on in their lives, such as walking and regular speech. Since there are many different neurological and behavioural features, a wide range of clinical assessments may need to be carried out. The most important is genomic screening, as the underlying cause for CES is genetic, but other techniques, such as echocardiograms and CT scans, can help establish where issues are in the baby. For people with varying behavioural and neurological symptoms, a well-rounded treatment plan is the best option, starting as early as possible to help the proper development of the child as they grow.