Cat Eye Syndrome (CES) is a rare congenital disorder that impacts multiple body systems. It is named for the distinctive eye defect, a vertical coloboma, which is present in about half of all affected individuals. CES is a highly variable condition, meaning the severity of symptoms can range from nearly unnoticeable to severe, life-threatening malformations.
The Chromosomal Abnormality
The underlying cause of Cat Eye Syndrome is a genetic rearrangement involving chromosome 22. CES results from a gain of genetic material on the long arm of this chromosome, typically the 22q11.2 region. This excess material often exists as a small supernumerary marker chromosome (sSMC), which is an extra, small chromosome in addition to the normal pair of 22s.
The presence of this sSMC leads to a partial tetrasomy, meaning there are four copies of the genes located on the duplicated segment of 22q11.1-q11.2 instead of the usual two. This duplication disrupts the normal balance of gene dosage, causing developmental defects. The extra marker chromosome often forms through an inverted duplication of the 22q11 region, and the size and exact location of the duplicated segment can differ between individuals, contributing to the broad spectrum of clinical features.
Key Clinical Manifestations
The physical features associated with Cat Eye Syndrome are diverse, but a triad of specific anomalies is frequently cited: preauricular anomalies, anal atresia, and ocular coloboma. Preauricular anomalies, which are small tags or pits located in front of the ear, are the most consistent feature of the syndrome, present in up to 85% of cases.
The characteristic eye defect, coloboma, involves a gap or fissure in the structure of the eye, often affecting the iris. This gives the pupil an elongated, “keyhole” or “cat-eye” appearance. The defect can extend to the retina or choroid, potentially causing vision impairment or light sensitivity, but it is absent in approximately half of all patients.
Anal atresia, the absence or obstruction of the anal opening, is another significant malformation seen in a high percentage of individuals with CES. It often requires immediate surgical correction and may be accompanied by a fistula, an abnormal connection between the rectum and other structures like the bladder or perineum.
Congenital heart defects are highly prevalent, affecting over half of those diagnosed, and their severity often dictates the long-term outlook. The most frequently reported severe cardiac malformation is total anomalous pulmonary venous return (TAPVR), where the pulmonary veins connect to the heart incorrectly. Other common heart issues include ventricular or atrial septal defects, which are holes in the walls separating the heart’s chambers.
Malformations of the urinary tract and kidneys are also common, ranging from absent or underdeveloped kidneys (agenesis or hypoplasia) to hydronephrosis (swelling due to urine backup). Craniofacial differences, such as a cleft lip or palate, down-slanting palpebral fissures, and a flat nasal bridge, may also be present. While intellectual disability is usually mild or borderline normal, developmental delays are a possibility. Nearly every organ system is potentially affected by CES.
Methods of Diagnosis and Inheritance Patterns
Diagnosis of Cat Eye Syndrome is typically suspected based on physical features and confirmed through genetic testing. Common tests used to identify the chromosomal abnormality include conventional karyotyping, which detects the extra marker chromosome. Fluorescence In Situ Hybridization (FISH) is frequently used to confirm the diagnosis by using fluorescent probes that target the duplicated 22q11 region.
For precise mapping of the genetic material, Chromosomal Microarray (CMA) or array Comparative Genomic Hybridization (aCGH) can determine the exact size and breakpoints of the duplicated segment. Prenatal diagnosis is possible through procedures like amniocentesis or chorionic villus sampling, followed by these genetic tests.
The majority of CES cases arise sporadically as a de novo mutation, meaning the chromosomal error occurs randomly and is not present in either parent’s other cells. Inherited cases are possible if a parent has a balanced translocation involving chromosome 22 or is a mosaic carrier. Genetic counseling is recommended for parents to assess recurrence risk and determine if a parental chromosomal abnormality exists.
Ongoing Medical Care and Support
Managing Cat Eye Syndrome requires a comprehensive, multidisciplinary approach because of the systemic nature of the malformations. The medical team typically involves a wide range of specialists, including cardiologists, nephrologists, ophthalmologists, and surgeons, who coordinate care based on the individual’s specific symptoms.
Surgical interventions are often necessary soon after birth to correct severe anatomical defects. This includes immediate repair for congenital heart defects, especially those like TAPVR, which can be life-threatening. Anal atresia requires timely surgical correction to establish a functional anal opening. Less urgent surgeries may address cosmetic concerns, such as the removal of preauricular tags or the correction of a cleft lip or palate.
Long-term monitoring with various specialists is required to track the condition and manage chronic issues. Regular echocardiograms and cardiology follow-ups monitor heart function. Nephrologists routinely assess kidney function due to the high likelihood of renal malformations. Ophthalmologists conduct frequent eye exams to manage coloboma-related issues, such as vision correction and prescription sunglasses for light sensitivity.
Developmental and therapeutic support improves the quality of life for individuals with CES. Early intervention services are beneficial, often beginning in infancy to address developmental delays or low muscle tone (hypotonia).
Therapeutic Support
- Physical therapy can help with gross motor skills.
- Occupational therapy assists with fine motor skills and sensory processing.
- Speech therapy may be necessary for those with communication difficulties or feeding issues related to craniofacial anomalies.
The long-term prognosis for Cat Eye Syndrome depends on the severity of the heart and kidney malformations, though many individuals with milder presentations can have a near-normal life expectancy.