Genetic disorder associated with an extra portion of chromosome 22, contributing to the development of Cat's Eye Syndrome.
News Article: Understanding Cat Eye Syndrome (CES): A Rare Genetic Disorder
Cat Eye Syndrome, also known as Schmid-Fraccaro syndrome, is a rare genetic disorder that affects approximately 1 in 50,000 to 100,000 people. This condition is caused by the presence of an extra, abnormal chromosome derived from chromosome 22, which contains duplicated or triplicated segments of genetic material.
The specific genetic changes involve a supernumerary marker chromosome, typically including partial tetrasomy (four copies) of a segment on the short arm and proximal long arm of chromosome 22, often denoted as 22q11.2. This extra chromosomal material increases gene dosage beyond the normal two copies.
Several dosage-sensitive genes within this region are implicated in the features of CES. Key genes and their impacts include:
- CECR1 (Cat Eye Syndrome Chromosome Region Candidate 1): Overexpression of this gene, thought to be involved in immune system regulation and vascular development, may contribute to congenital heart defects, a common feature in CES.
- CECR2: This gene plays a crucial role in chromatin remodeling and embryonic development. Increased dosage may impact neurological and craniofacial development.
- Genes related to the 22q11.2 region also overlap with genes implicated in DiGeorge Syndrome, suggesting that their dysregulation affects cardiac, immune, and craniofacial structures.
The health and developmental impacts commonly observed in CES due to these genetic alterations include:
- Coloboma of the iris (the “cat eye” feature): A hole or defect in the iris caused by developmental disruption, present in approximately half of CES individuals.
- Anal atresia or perineal abnormalities
- Congenital heart defects: Such as total anomalous pulmonary venous return (TAPVR) or other malformations.
- Ear anomalies and hearing loss
- Developmental delays and intellectual disability are variable but reported due to neurological involvement.
- Additional features like kidney malformations and skeletal anomalies also arise from gene dosage imbalances in this region.
In most cases, CES occurs by chance in early development with no prior family history (de novo formation). However, when parental transmission occurs, it typically involves a parent who carries an extra circular or rod-shaped small supernumerary marker chromosome (sSMC).
CES patients may also experience congenital kidney and digestive system issues, requiring lifelong treatment. Genes like SLC7A4, which helps transport amino acids, and TXNRD2, which affects the balance of harmful and protective molecules inside cells, are linked to these complications.
Other distinctive features of CES include preauricular tags or pits, found near the ears, present in 81% of CES patients and usually harmless. Some patients may also experience congenital heart diseases, such as atrial septal defects, that may require surgical correction.
In summary, CES results from the presence of an extra chromosome 22 segment causing increased dosage of critical developmental genes within 22q11 that disturb heart, eye, ear, and craniofacial development, leading to the characteristic physical malformations and potential developmental challenges.
