Roberts+Syndrome

Roberts Syndrome

Roberts syndrome is a very rare autosomal recessive disease, affecting just 150 known individuals. It occurs due to a mutation in the ESCO2 gene (Establishment of Sister Chromatid Cohesion N-acetyltransferase 2). This gene, on chromosome 8, functions to hold sister chromatids together before chromosomal separation occurs in cell division. When sister chromatids lack the glue-like protein between them that ESCO2 encodes for, the cell slows or even stops cell division altogether because of this anomaly. This leads to the degradation or destruction of the daughter cells. **[1]**
 * Description of disease:**

Individuals with the disease display numerous deformities to their face and limbs. These can include, but are not limited to, shortened and underdeveloped limbs, missing fingers or toes, small head, cleft lip, cleft palate, eyes set far apart, ears set low, small and pointed nose, and possibly a brain protrusion at the forehead. Symptoms can also include mental retardation, as well as defects of the heart, kidneys, and genitals. **[1]** Individuals born with this disease may be stillborn or survive for only a short time after birth. The mortality rate for Roberts syndrome is high, but other individuals with less severe case may live to reach adulthood. **[1]**

To be officially diagnosed with this disease, cytogenetic testing is done to analyze the ESCO2 gene. This displays the abnormalities that occur during chromosomal separation. **[2]**



Fig. 1 Phenotype of typical Roberts Syndrome patient **[3]** []

__**Flowchart**__



Fig. 2. Flowchart of onset of Roberts Syndrome

__**Fact-sheet**__

Roberts Syndrome
 * Name of disease:**

Mutation of the ESCO2 gene. (Establishment of Sister Chromatid Cohesion N-acetyltransferase 2).
 * Root cause:**

Anything that normally uses the protein encoded for by ESCO2.
 * Affected cell types/tissues/organs/systems:**

-1919, John Roberts discovered an Italian family and described the symptoms of Roberts Syndrome in all three children who were the offspring of first cousin parents. -1969, J Herrmann and his associates also found patients with symptoms of Roberts Syndrome, and stated that the disease was autosomal recessive. He named it SC syndrome because of the last names of the patients. Later it was realized that these syndromes were the same. **[2]**
 * Historical Background:**

Limb and craniofacial abnormalities Ex: underdeveloped limbs, small head, cleft lip/palate, facial defects, mental retardation, heart, kidney, genital defects. **[1]**
 * Common Symptoms:**

No cure. Treatments work to aid symptoms and improve quality of life. Surgeries may be done to help fix deformities. May receive prosthetic limbs, speech therapy, and treatments for heart and or kidney problems. **[2]**
 * Standard Treatments:**


 * Current Research:**

Current research includes using a method of complementation to counteract the dysfunction of the ESCO2 gene. If the heterochromatic repulsion caused by lack of the protein ESCO2 encodes for was able to be complemented, it may reverse the abnormalities. The researchers in this article used a transient chromosome-transfer assay and homozygosity mapping to screen the whole genome. They found that there was a locus on chromosome 8, the same chromosome where ESCO2 is located, that can possibly offer phenotypic correction by complementing the heterochromatic repulsion defect **[5]**.

The Cohesin complex is a group of proteins that help in the connection and separation of sister chromatids. When this complex is not functioning correctly, major problems in cell division can occur. An example of a major problem is Roberts Syndrome where there is a mutation of the ESCO2 gene causing the degradation and or destruction of daughter cells. The researchers in this article work to describe how cohesin is involved in the regulation of transcription and how it works to aid in DNA repair as well as creating a stable genome **[4]**.


 * Citations:**
 * [1] []**
 * [2] []**
 * [3]** []
 * [4]** Dorsett, D., & Strom, L. (2012). The Ancient and Evolving Roles of Cohesin in Gene Expression and DNA Repair. //Current Biology//, //22//(7), R240-R250. Retrieved from DOI: 10.1016/j.cub.2012.02.046
 * [5]** McDaniel, L., Tomkins, D., Stanbridge, E., Somerville, M., Friedberg, E., & Schultz, R. (2005). Mapping of a Single Locus Capable of Complementing the Defective Heterochromatin Phenotype of Roberts Syndrome Cells. //AJHG//, //77//(1), 132-139. Retrieved from DOI: 10.1086/431328