Cat Eye Syndrome (CES) is a rare chromosomal disorder present at birth, affecting an estimated 1 in 50,000 to 150,000 live births. It results from extra genetic material from chromosome 22, typically a duplicated segment of the short arm and a small part of the long arm, leading to a partial trisomy or tetrasomy of that region. The defining characteristic of CES is its highly variable clinical presentation, meaning symptoms can range significantly from being very mild to severe and impacting multiple organ systems.
Characteristic Eye and Ear Features
The name Cat Eye Syndrome is derived from a specific eye abnormality, known as ocular coloboma, which is present in about 40% to 60% of affected individuals. A coloboma is a gap or cleft in the structure of the eye that occurs when the fissure fails to close during early fetal development. When this defect affects the iris, it creates a distinctive keyhole or vertical slit appearance, resembling a cat’s eye.
This eye defect can also involve the retina, choroid, or optic nerve, and in severe cases, a coloboma can significantly impair vision. Other ocular features include small eyes (microphthalmia), misalignment of the eyes (strabismus), or clouding of the cornea. The most consistent physical features of CES are related to the ears, specifically preauricular anomalies, which are found in approximately 75% to 81% of patients.
These ear anomalies typically present as small growths of skin called preauricular tags, or slight depressions known as preauricular pits, located just in front of the outer ear. More serious defects, such as a severely reduced external ear (microtia) or a closed external auditory canal (atresia), can also occur. Hearing impairment, often conductive hearing loss, can result from these structural abnormalities.
Major Cardiac and Renal System Abnormalities
The internal malformations associated with Cat Eye Syndrome can be life-threatening. Congenital heart defects are reported in about half of all cases and involve structural problems. Common cardiac issues include holes between the chambers of the heart, specifically atrial and ventricular septal defects.
One frequently observed heart defect in CES is Total Anomalous Pulmonary Venous Return (TAPVR), where the veins bringing oxygenated blood from the lungs connect to the wrong chamber of the heart. Defects like Tetralogy of Fallot, a complex condition involving four distinct heart defects, or an interrupted aortic arch may also be present. Surgical correction is often necessary to treat these serious cardiac malformations.
Abnormalities of the renal (kidney) and urinary systems are also common, occurring in 20% to 40% of individuals with Cat Eye Syndrome. These can range from one or both kidneys being underdeveloped (hypoplasia) or completely absent (agenesis). Other defects include a duplicated collecting system or a condition where urine buildup causes the kidney to swell (hydronephrosis).
Gastrointestinal and Skeletal Manifestations
Malformations of the lower gastrointestinal tract are a significant feature of Cat Eye Syndrome, with anorectal malformations reported in 30% to 50% of patients. The most common of these is Anal Atresia, characterized by the anal opening being absent or abnormally narrow. This condition requires immediate surgical intervention to correct the obstruction and allow for normal bowel function.
While less frequent, other gastrointestinal issues such as the failure of bile ducts to develop normally (biliary atresia) or malrotation of the intestines have also been documented. Skeletal differences are associated with the syndrome and can affect various parts of the body. These include spinal defects like an abnormal curvature (scoliosis) or the abnormal fusion of vertebrae.
Minor limb differences, such as small defects in the hands or feet, or hip dislocation, can also occur. These skeletal and structural issues often require orthopedic evaluation and management. The combination of these differences adds to the overall complexity of the clinical picture.
Understanding Symptom Variability and Developmental Impact
The clinical presentation of Cat Eye Syndrome demonstrates heterogeneity, meaning the extent and severity of symptoms are unpredictable. Some individuals may only exhibit the mildest features, such as isolated preauricular tags, and experience no major organ involvement. Conversely, others face a severe, multi-system disorder involving life-threatening cardiac and renal defects.
This wide spectrum of symptoms makes establishing a prognosis challenging, as the outcome depends entirely on which organs are affected. Regarding developmental impact, many individuals with Cat Eye Syndrome are reported to have normal or near-normal intellectual development. However, intellectual disability can occur, typically presenting as mild to moderate impairment in approximately 30% of cases.
Severe intellectual disability is considered a rare outcome. The variability in symptoms is thought to be related to the specific size and nature of the extra genetic material from chromosome 22. However, a clear correlation between the duplication size and the severity of symptoms has not been established, emphasizing the need for comprehensive screening upon diagnosis.