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=Blooms Syndrome= toc = = = = =Name of Condition= Blooms Syndrome or Congenital Telangiectatic Erythema

**Description **
 Blooms Syndrome is an inherited disorder characterized by short stature, sun-sensitive skin changes, and other health problems (Blooms Syndrome, 2010). It is an autosomal recessive disorder associated with dwarfism, immunodeficiency, reduced fertility, and elevated levels of many types of cancer (Karow, Constantinou, Li, & West, 2000). The syndrome was first recognized and described as a clinical syndrome by Dr. David Bloom (German, 1969). He took his original observations and decided that there were three distinct features that were associated with the syndrome. The disease is currently very rare but it is found mostly in people of Central and Eastern European (Ashkenazi) Jewish background (Blooms Syndrome, 2010).

**History of the Disease **
 As mentioned before, Blooms Syndrome was first recognized by Dr. David Bloom in 1954. The first results were taken in 1966 where Dr. Bloom took twenty- seven patients that he felt had acquired the disease and by the three observations that he determined were part of the disease. In the twenty-seven patients that Bloom was observing, ten of which were females making the other seventeen males. In the infected patients, none of the parents showed symptoms of the disease making them carriers (German, 1969). In his study, he found that most all the patients were of Eastern European decent.

**Symptoms **
 The three cardinal features that Bloom described consist of defects in the butterfly regions of the face, sun sensitivity, and finally stunted growth. The defects of the butterfly region of the face effect areas such as the cheeks, nose, eye lids, nose lips, forehead, having a narrow cranium tiny jaw (German, 1969). A study took place on two brothers from native Kashmiri and some of the defects that both of them had were blistering and scarring that were all over the face (Sultan & Sultan, 2010).The ears or patients may be small but stick out (Ellis & German, 2002). The skin often appears burnt in the summertime and usually better when protected from it. The skin starts to become to have less of a severe reaction to as the individual gets older, but some scarring can permanently take place as what was show in the one of brothers below. (figure 1) Also the eyebrows and eyelashes start to become deformed.

(Figure 1. Kashmiri brother with blisters and scarring)

The final defect that Bloom observed that seems to be the most prelevant and obvious of the three is the stunted growth. The average size of the human is well below average through the stages of life (German, 1969). The body is fairly proportional except for the slightly smaller head. The average birth weight children affected with the disease is about 4.2 pounds and the average height for an affected adult is 4’7” (Ellis & German, 2002).  Though those are the three major features that describe Blooms, recently since Bloom himself conducted the research, other defects have become common. A few that can be mentioned are Familial clustering or consanguinity. This is when those getting married are from the same ancestors. The Jewish ancestry has suggested a recessive pattern of inheritance to this (Ellis & German, 2002). As you can see from the pedigree below as men and women begin to marry within the same blood, this is when the mutation takes place and the syndrome becomes expressed.

 (Figure 2 shows a pedigree with the parents being from the same ansectery causing the mutation)

Next, cytogenetic studies in individuals have shown a consistent abnormality in cells in vitro. This is a tendency to chromosomal breakage and rearrangement (Ellis & German, 2002). This is a very difficult topic to explain but here goes nothing. In the simplest terms, chromosome mutations are present in gaps and rearrangements. Chromatic exchange occurs in Blooms Syndrome which is evidence of somatic crossing over. In turn, the somatic cell has an increased risk to become homozygous (German, Roe, Leppert, & Ellis, 1994)  The final symptom that has become the most talked about is that of malignancy. Because the parents of the effected have the same ancestry in them, that is going to lead to mutations in the genes. This will then cause the normal cell matter to be lost in simplest terms causing an abnormal degree of proliferation of that cell (Yankiwski, Marciniak, Guarente, & Neff, 2000). Hence the cancer causing.

**Diagnosis **
The diagnosis of Bloom's syndrome can be confirmed by a lab test known as a chromosome study. The skin and bloom cells show a characteristic pattern of chromosome rearrangement. Recently, the gene for Bloom's syndrome was isolated. The gene is located on chromosome 15. A particular mutation in the gene has been identified as the cause of Bloom's syndrome in a lot of Ashkenazi Jews. Because of these recent findings, carrier testing and pre-birth diagnosis for Bloom's syndrome are available (America, 2011).

**Treatment **
There is no current treatment for the Bloom's syndrome so the only thing to dry to do is prevent it. Adults with Bloom's syndrome should be a little more concerned and aware about cancer forming. Having regular check-ups with your physician and looking out for the possible symptoms are two ways that help. Although growth hormone therapy has been attempted to increase height in children with Bloom's syndrome, it does not appear to work (Thomas, Shanley, Walker, & Eeles, 2008). In addition, there is some concern that the use of growth hormone may increase the risk for later cancer forming cells (America, 2011).

**<span style="background-color: white; font-family: Arial,sans-serif; font-size: 12pt;">Management **
<span style="background-color: white; font-family: Arial,sans-serif; font-size: 12pt;">The facial skin lesion should be kept out of the sun whenever possible. Wearing hats, sunglasses and putting on appropriate sunscreen are a must if going outside. Cancerous symptoms are another huge management that needs to be done. During childhood, when leukemia is the main neoplasm happening, no present surveillance takes place (Karow, Constantinou, Li, & West, 2000). In adulthood, however, extra attention needs to take place to permit early diagnosis of tumors. Those cancers that usually depend on their prompt surgical removal can be taken care of if watched. Procedures in general use for early diagnosis of cancer such as mammography, Pap smears, and colonoscopy may be begun earlier in life than usual (Karow, Constantinou, Li, & West, 2000). Because bone marrow transplantation sometimes is useful in treating cancer of certain types, a potential marrow donor can be attempted. If future non-BS pregnancies occur, stem cells can be harvested from the placental blood and stored frozen (America, 2011).

**<span style="background-color: white; font-family: Arial,sans-serif; font-size: 12pt;">Inheritance **
<span style="background-color: white; font-family: Arial,sans-serif; font-size: 12pt;">Bloom Syndrome is an autosomal recessive expressed that is extremely rare that is found on chromosome 15 and caused by a mutation of the gene BLM (Yankiwski, Marciniak, Guarente, & Neff, 2000). The protein encoded by the normal gene has DNA helicase activity and functions in the maintenance of genomic stability. Increased sister chromatid exchanges and chromosomal instability also occur, which is assumed to be responsible for the phenotype and the cancer predisposition.

<span style="background-color: white; font-family: Arial,sans-serif; font-size: 12pt;"> More than 170 case reports of Bloom syndrome have been made. The frequency of parental consanguinity is much greater with this syndrome than in the general population (Sultan & Sultan, 2010). It is more common in Ashkenazi Jews, but has been reported in Japan and other countries right at birth and young ages (Bajoghli & Elston, 2009). Those affected with Bloom Syndrome have a one in four chance (25%) of having a child to inherit the disease as well shown below. <span style="background-color: white; font-family: Arial,sans-serif; font-size: 12pt;"> (Figure 3 shows that ¼ will only be affected. “RED”)

**<span style="background-color: white; font-family: Arial,sans-serif; font-size: 12pt;">Molecular Basis of Bloom’s **
<span style="background-color: white; font-family: Arial,sans-serif; font-size: 12pt;">Mutations <span style="font-family: Arial,sans-serif; font-size: 12pt;">in BLM, which encodes a RecQ helicase, give rise to Bloom’s syndrome, a disorder associated with cancer predisposition and genomic instability. A defining feature of Bloom’s syndrome is an elevated frequency of sister chromatid exchanges. These arise from crossing over of chromatid arms during homologous recombination (Karow, Constantinou, Li, & West, 2000). This is a bit different than regular crossing over. It is a process that exists to repair DNA double-stranded breaks and damaged replication fork (Wu & Hickson, 2003). Whereas crossing over is required in meiosis, in mitotic cells it can be associated with detrimental loss of heterozygosity (Wu & Hickson, 2003). <span style="font-family: Arial,sans-serif;">When a cell prepares to divide to form two cells, the DNA that makes up the chromosomes is copied so that each new cell will get a complete set of chromosomes (Brooker, 2012)**.** The copied DNA from each chromosome is arranged into two identical structures, called sister chromatids, which are attached to one another during the early stages of cell division. Sister chromatids then exchange small sections of DNA (Brooker, 2012).

**<span style="background-color: white; font-family: Arial,sans-serif; font-size: 12pt;">Recent Advances in Research **
<span style="font-family: Arial,sans-serif; font-size: 12pt;">Scientists studying the disease have recently discovered a new molecular technique for tumorigenesis based on a DNA enzyme (Karow, Newman, Freemont, & Hickson, 1999). A mutated form of this enzyme is thought to cause the type of chromosome breakage that can lead to many tumors. A team led by Nathan Ellis and James German at the New York Blood Center identified the enzyme from tissue samples from patients with Bloom's syndrome, a rare cancer syndrome with less than 180 documented cases worldwide (Ellis & German, 2002). <span style="font-family: Arial,sans-serif; font-size: 12pt;">(Figure 4 shows chromosome 15 breaking and rearranging. This is the cause for the mutation.)

<span style="font-family: Arial,sans-serif; font-size: 12pt;">The sequence of the gene, //BLM// that codes for the enzyme that is altered in Bloom's syndrome shows great similarity to a family of DNA-handling proteins called RecQ helicases which are found in bacteria and yeast (Dickman, 1996). These enzymes are involved in the process of opening up double-stranded RNA and DNA to make it accessible for copying, transcription and repair. This could serve as a basis for diagnosing tissues at risk for cancer or for developing prophylactic or therapeutic agents against cancer (Dickman, 1996).

**<span style="background-color: white; font-family: Arial,sans-serif; font-size: 12pt;">Population Genetics **
<span style="font-family: Arial,sans-serif; font-size: 12pt;">The disorder is more common in people of Central and Eastern European (Ashkenazi) Jewish background, which about 1 in 50,000 are affected.

**<span style="background-color: white; font-family: Arial,sans-serif; font-size: 12pt;">Additional Resources **
<span style="background-color: white; font-family: Arial,sans-serif; font-size: 12pt;">If you have any questions about the syndrome, you can go to this website and type in the question you have <span style="font-family: Arial,sans-serif; font-size: 12pt;">[]

<span style="background-color: white; font-family: Arial,sans-serif; font-size: 12pt;"> Feeling generous? Here is the official website to donate money for research that is being conducted on Bloom’s syndrome <span style="font-family: Arial,sans-serif; font-size: 12pt;">[]

**<span style="background-color: white; font-family: Arial,sans-serif; font-size: 12pt;">Resources **
America, J. F. (2011). //Blooms Syndrome//. Retrieved November 28, 2011, from Jewish Philly: http://www.jewishphilly.org/page.aspx?id=72434

Bajoghli, A., & Elston, D. (2009). Bloom Syndrome (Congenital Telangiectatic Erythema). //Medscape Reference//.

//Blooms Syndrome//. (2010, November). Retrieved November 30, 2011, from Genetics Home Reference: http://ghr.nlm.nih.gov/condition/bloom-syndrome

Brooker, R. J. (2012). //Genetics Analysis and Principles.// New York: McGraw-Hill.

Ciocci, S., Ellis, N., Proytcheva, M., Lennon, D., Groden, J., & German, J. (1998). The Ashkenazic Jewish Bloom Syndrome Mutation blmAsh Is Present in. //American Journal of Human Genetics//, 1685-1693.

Dickman, S. (1996). Bloom's syndrome enzyme leads to a new cancer mechanism. //Oxford Journals//, 2-6.

Ellis, N., & German, J. (2002). Bloom Syndrome. In B. Vogelstein, & K. W. Kinzler, //The Genetic Basis of Human Cancer// (pp. 267-288). McGraw- Hill.

German III, J. L., Sanz, M., & Passarge, E. (n.d.). //Blooms Syndrome//. Retrieved November 28, 2011, from Blooms Syndrome Resistry: http://www.bloomssyndrome.org/bloomssyndrome.htm

German, J. (1969). Bloom's syndrome. I. Genetical and clincical observations in the first twenty-seven patients. //The American Journal of Human Genetics//, 196-227.

German, J., Roe, A., Leppert, M., & Ellis, N. (1994). Bloom syndrome: an analysis of consanguineous families assigns the locus mutated to chromosome band 15q26.1. //Proceedins of the National Academy of Sciences of the United Sates of America//, vol 91.

Karow, J., Newman, R. H., Freemont, P. S., & Hickson, I. D. (1999). Oligomeric ring structure of the Bloom's syndrome helicase. //Current Biology//, 597-600.

Shimura, T., Torres, M. J., Martin, M. M., Rao, V. A., Pommier, Y., Katsura, M., et al. (2008). Bloom's syndrome helicase and Mus81 are required to induce transient double strand DNA breaks in response to DNA replicatioin stress. //National Institutes of Health Public Access//, 1152-1164.

Shiraishi, Y., Yosida, T., & Sandberg, A. (1985). Maligant transformation of bloom syndrome B-lymphoblastoid cell lines by carcinogens. //Proceedings of the National Academy of Sciences of the United States of America//, 5102-5106.

Sultan, S. J., & Sultan, S. T. (2010, March 1 ). Pediatric Dermatology. //Bloom Syndrome in Two Siblings//, pp. 174-177.

Thomas, E., Shanley, S., Walker, L., & Eeles, R. (2008). Surveillance and Treatment of Malignancy. //Clinical Oncology//, 375-379.

Wu, L., & Hickson, I. (2003). The Bloom's syndrome helicase suppresses crossing over during homologous recombination. //Nature//, 870-874.

Xu, D., Guo, R., Sobeck, A., Bachrati, C., Yang, J., Enomoto, T., et al. (2008). RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability. //Genes and Development//, 2843-2855.

Yankiwski, V., Marciniak, R. A., Guarente, L., & Neff, N. F. (2000). Nuclearstructure in normal and Bloom syndrome cells. //Proceedings of the National Academy of Sciences of the United States of America//, 5214-5219.