Cat Eye Syndrome, also known as Schmid-Fraccaro syndrome, is a rare chromosomal disorder. Our genetic blueprint is organized into 23 pairs of chromosomes, numbered 1 through 22, plus the sex chromosomes (X and Y). A healthy person has 46 chromosomes total. An individual with Cat Eye Syndrome has a small, extra chromosome, resulting in 47 chromosomes instead of 46.

This extra chromosome is known as a marker chromosome. It is not a complete extra chromosome, but rather a fragment made up of duplicated genetic material from a specific part of chromosome 22. The duplicated segment includes the entire short (p) arm and a small piece of the long (q) arm of chromosome 22. Because the individual has their two normal copies of chromosome 22 plus this extra piece (which contains two inverted copies of the region), they have a total of four copies of this specific genetic material. This is sometimes called a partial tetrasomy 22.

To understand this, it is helpful to use an analogy. Think of your complete set of 46 chromosomes as a 46-volume encyclopedia containing all the instructions for building and running a human body.

• In Cat Eye Syndrome, an error occurs during the “printing” process.
• An extra, small booklet is created, containing a photocopied and stapled-together version of the first chapter from Volume 22.
• This extra booklet (the marker chromosome) is now present in every cell. The body becomes confused by having four copies of these specific instructions instead of the normal two.
• This “overdose” of genetic information disrupts the normal, orderly development of several body systems, particularly the eyes, ears, heart, kidneys, and anorectal region.

In my experience, parents are often unfamiliar with Cat Eye Syndrome until after birth, when distinctive facial features or other congenital findings prompt genetic evaluation.

The direct cause of Cat Eye Syndrome is the presence of this extra marker chromosome containing duplicated material from the 22q11 region. This duplication of genes disrupts the normal signaling and developmental pathways during embryonic and fetal growth. The specific genes located within this region are responsible for the proper formation of many different tissues. Having extra copies of these genes leads to the wide range of birth defects and physical characteristics seen in the syndrome. The precise reason why this chromosomal error occurs during the formation of reproductive cells is not known.

Clinically, I’ve seen that the condition is caused by the presence of an extra chromosome fragment (an inverted duplicated chromosome 22), which is typically a random genetic event, not inherited.

Cat Eye Syndrome is a chromosomal condition that is present from birth. It is not contagious. Its origin is a genetic error that can be either spontaneous or, in rare cases, inherited.

• Sporadic (de novo) Event: In the vast majority of cases, Cat Eye Syndrome is sporadic. This means the error that creates the extra marker chromosome occurs as a random, new (de novo) event during the formation of the egg or sperm cells in a healthy parent. There is nothing the parents did or did not do to cause this to happen, and the risk of them having another child with the same condition is very low.
• Inherited Form: In a minority of cases, the marker chromosome can be passed down from a parent who also has Cat Eye Syndrome. Because the condition is so variable, a parent may have very mild features and be unaware they have the syndrome until their more significantly affected child is diagnosed. The inheritance risk from an affected parent can be complex but can be as high as 50% for each pregnancy. Genetic counseling is essential for affected families.

In my experience, Cat Eye Syndrome isn’t passed down through families. In most cases, it’s the result of a rare chromosomal error that occurs during cell division in early pregnancy.

The most important feature of Cat Eye Syndrome is its extreme clinical variability. No two individuals are affected in exactly the same way. Some people may have only one or two mild features and normal intelligence, while others may have multiple, severe congenital abnormalities.

The condition is classically described by a triad of features, although not everyone will have all three:

1. Coloboma of the Iris: This is the feature that gives the syndrome its name. A coloboma is a gap or defect in the eye structure. In CES, this often affects the iris (the colored part of the eye), causing the pupil to appear elongated and teardrop- or keyhole-shaped, which can resemble the vertical pupil of a cat. Colobomas can also affect other parts of the eye, like the retina or optic nerve, and may or may not impact vision.
2. Anal Atresia or Stenosis: This is a birth defect where the anal opening is either absent (atresia) or very narrow (stenosis), which requires surgical correction.
3. Preauricular Pits or Tags: These are small skin tags or shallow pits located in front of the ears.

In addition to this classic triad, individuals with Cat Eye Syndrome can have a wide range of other features affecting many body systems.

• Craniofacial Features: These can include downward-slanting eyes, widely spaced eyes (hypertelorism), a small jaw (micrognathia), and a cleft palate.
• Congenital Heart Defects: These are very common, affecting about half of all individuals. A variety of defects can occur, with Total Anomalous Pulmonary Venous Return (TAPVR) and Tetralogy of Fallot being among the most common.
• Kidney and Urinary Tract Abnormalities: This is also a very common feature. An individual may be born with a missing kidney (renal agenesis), an underdeveloped kidney (renal hypoplasia), or other structural problems.
• Skeletal Problems: Curvature of the spine (scoliosis) and abnormalities of the ribs or vertebrae are common.
• Growth: Many children with CES have a slower growth rate and may have short stature.
• Intellectual Development: This is a crucial point of variability and hope for many families. While some individuals have moderate to severe intellectual disability, many, if not most, people with Cat Eye Syndrome have normal or only borderline-to-mild intellectual disability.

I’ve seen a wide range of presentations from minor cosmetic findings to serious organ involvement. Common signs include coloboma (eye defect), anal malformations, and heart defects.

A diagnosis of Cat Eye Syndrome may be suspected prenatally if an ultrasound reveals characteristic findings like a heart or kidney defect. After birth, it is usually suspected when a newborn presents with a combination of the physical features, such as an eye coloboma and an anal anomaly.

The diagnosis is confirmed by chromosome analysis from a blood sample.

• Karyotype: This is a laboratory test that creates a picture of a person’s chromosomes. In an individual with CES, the karyotype will show the normal 46 chromosomes plus one small, extra marker chromosome (47, +mar).
• Fluorescence In Situ Hybridization (FISH): To confirm that the extra marker chromosome is derived from chromosome 22, a specialized test called FISH is used. It uses a fluorescent probe that is specifically designed to “light up” the 22q11 region. When applied to the patient’s chromosomes, the probe will light up the two normal copies of chromosome 22 and the extra marker chromosome, confirming the diagnosis of Cat Eye Syndrome.
• Chromosomal Microarray: This advanced genetic test can also be used to identify the duplication and determine its precise size.

Once a diagnosis is made, a child must undergo a comprehensive evaluation by a team of specialists to screen for all potential associated medical issues. This will always include a detailed echocardiogram of the heart, an ultrasound of the kidneys, a thorough eye examination, and a hearing test.

In my experience, physical signs alone aren’t enough, identifying the extra chromosome 22 material under the microscope provides definitive diagnosis and guides family counseling.

There is no cure for Cat Eye Syndrome because the underlying chromosomal abnormality cannot be changed. Management is entirely supportive and symptomatic, focused on treating the specific medical issues and developmental challenges that each individual faces. This requires a lifelong, coordinated effort from a multidisciplinary team of specialists.

The care team for a child with CES may include:

• A pediatrician and a clinical geneticist
• A pediatric cardiologist
• A pediatric nephrologist (kidney specialist)
• A pediatric surgeon
• An ophthalmologist and an audiologist
• Physical, occupational, and speech therapists

The key management strategies include:

• Surgical Correction of Congenital Defects: This is often the first and most urgent step. Surgery is frequently required in infancy to repair major heart defects or to correct anal atresia.
• Management of Kidney Problems: A nephrologist will monitor kidney function and manage any structural abnormalities or reflux of urine.
• Vision and Hearing Support: An ophthalmologist will manage any vision problems associated with colobomas. Hearing aids may be needed for hearing loss.
• Developmental Therapies: Early and continuous intervention is the cornerstone of helping a child reach their full developmental potential. This includes:
  • Physical therapy to help with motor skills and balance.
  • Occupational therapy to help with fine motor skills and daily living activities.
  • Speech therapy to address any language delays.
• Educational Support: Many children with CES will benefit from an individualized education plan (IEP) and special education services to support their unique learning needs in school.

I’ve seen that treatment is tailored to the individual, this may include surgeries for anatomical defects, early developmental therapies, and regular follow-up with specialists.

Cat Eye Syndrome is a rare and highly variable chromosomal disorder that presents a unique set of challenges for affected individuals and their families. It is caused by the presence of an extra marker chromosome containing duplicated material from chromosome 22, which disrupts normal development. The journey often involves managing multiple medical issues, particularly heart and kidney defects, through a coordinated team of specialists. While the condition is lifelong, it is important to remember that the spectrum of outcomes is incredibly broad. Clinically, I emphasize to families that while this condition can be complex, proactive monitoring and intervention can help many children reach their developmental potential.

National Organization for Rare Disorders (NORD). (2023). Cat Eye Syndrome. Retrieved from https://rarediseases.org/rare-diseases/cat-eye-syndrome/

National Institutes of Health, Genetic and Rare Diseases Information Center (GARD). (2023). Cat eye syndrome. Retrieved from https://rarediseases.info.nih.gov/diseases/6004/cat-eye-syndrome

Chromosome Disorder Outreach Inc. (n.d.). Cat Eye Syndrome. Retrieved from https://chromodisorder.org/22/cat-eye-syndrome/