A Human Disorder, Involving Dysregulation of Epigenetic Mechanisms - Essay Example

BECKWITH-WIEDMANN SYNDROME. By of the of school Beckwith-Wiedemann syndrome (BWS) is a human disorder that involves of epigenetic mechanisms (Benacerraf, et al, 2007 pg 53). BWS is a condition that affects several parts of the body. It is categorized as an overgrowth syndrome, meaning that the affected infants are generally larger than normal (macrosomia) and keeps on growing and gaining weight at a rate that is unusual during childhood. Growth starts to slow around the age of 8, and adults having this condition are not unusually tall (Lovell, et al. 2006 pg 25). In some kids with BWS, given parts of the bady can grow abnormally large, resulting to uneven or an asymmetric appearance known as hemihyperplasia. A lot of people having this condition are born with an aperture in the abdomen wall that facilitates the protrusion of the abdominal organs through the navel. Many infants with BWS have tongues that are abnormally long (macroglossia) which can interfere with swallowing, breathing, and speaking. BWS’s other features include abdominal organs that are abnormally large (viscreromegaly), pits or creases in the skin near the ears, kidney abnormalities, and low blood sugar (hypoglycemia) in infant (Baum, et al, 2007 pg 78). The genetic causes of BWS are complex. It results from regulation of genes that is abnormal in a given region of chromosome 11. People usually inherit a single copy of this chromosome from each parent. In many genes of chromosome 11, each of the two copies of the genes is expressed (turned on) in the cells. However, for some genes, only the gene inherited from the father (paternal copy) is expressed while for some, the copy inherited from the mother (maternal copy) is the only one expressed (Michels, et al. 2012 pg 159). These parent specific differences in the expression of the gene are caused by genomic imprinting phenomenon. Abnormalities which involve genes on chromosome 11 that experience genomic imprinting are the cause of many cases of BWS. Typically, half of the cases are at least caused by changes in the methylation process. In genes that experience genomic imprinting, methylation is among the ways that parents of the gene of the origin are marked at the time of the creation of the egg and sperm cells (Gilbert, et al. 1999 pg 87). BWS is normally associated with the regions of DNA on chromosome 11 changes known as imprinting control regions (ICRs). ICRs guides the methylation of many genes that are associated with the normal growth, including the H19, CDKN1C, KCNQ1OT1, and IGF2 genes. The regulation of these genes is disrupted with abnormal methylation, which results to overgrowth and other characteristic features of BWS (Copel, J. A. 2012 pg 123). Around 20% of the cases of BWS are caused by paternal uniparental disomy (UPD) which is a genetic change. It causes people to poses two active copies of paternally expressed imprinted genes instead of one active copy from the father and one that is inactive from the mother. These people also don’t have genes that are active only on the chromosome’s maternal copy. BWS, paternal UPD normally occurs in the beginning in embryonic establishment and only affects some parts of the body, a phenomenon called mosaicism. Mosaic paternal UPD results to an imbalance in active paternal and maternal genes on chromosome 11 that underlines the symptoms and signs of the disorder. Unusually, mutations in the CDKNIC gene cause BWS. This gene gives instruction of protein making that assists guide growth before birth. Mutations in the CDKN1C gene stops this protein against restricting growth, which results to the abnormalities characteristic of BWS(Engel, et al. 2001 pg 37). People with BWS may increase at a very high rate at the time of the latter half of pregnancy and in life’s first few years. Growth that is abnormal may be manifested as hermihypertrophy and/or macroglossia. Hypoglocemia is reported to around 50% of babies with BWS. The frequency of medical complication and malformations is on the rise, including wall defects in the abdominal (umbilical hernia, omphalocele, and diastasis recti) and visceromegaly that involves liver, pancreas, spleen, adrenals, or kidneys. Fetal adrenocortical cytomegaly is a finding that is pathognomonic. Renal anomalies may involve primary malformations, nephrolithiasis, renal medullary dysplasia, and nephrocalcinosis. The predisposition to embryonal malignancies, with hepatoblastoma and tumor the most common (Chung, et al 2110 pg 84). There are no comparative requisites for the clinical diagnosis of BWS. It is accepted that the availability of at least three, or two, or one major finding(s) support a clinical diagnosis (Eentezami, et al. 2004 pg 73). However, it is critical to acknowledge the heterogeneous expression of the disorder and the part of positive molecular tests that may establish the diagnosis even in cases with little cardinal clinical features. Anticipatory medical management, more so with respect to tumor surveillance is supposed to be considered even for ‘milder’ presentation, e.g. umbilical hernia and prominent tongue. As well, a fraction of cases of IH, a clinical diagnosis distinct from BWS, reveal molecular etiologies extending over with BWS and parallel risks for development of embryonal tumor. Molecular testing is important in establishing the diagnosis of BWS but can’t at this moment, rule it out. This is due to negative results of the test that only reflect a failure to identify the underlying molecular in the tissue sampled alteration (Walterhouse, D. O. 1997 pg 77). The management of BWS patients basically involves standard surgical strategies and supportive medical. In addition, medical management for anticipatory for given findings should be carried out if the diagnosis of BWS is confirmed or even suspected (Cassidy, et al. 2011 pg 164). Whenever there are prenatal findings suggestive of or diagnostic for BWS, hypoglycemia screening should be carried out in the initial few days of life. In addition, parents are supposed to be advised of the clinical manifestations of hypoglycemia whenever it manifests after discharge from hospital (Wilson, et al. 2000 pg 124). In conclusion, it is expected that a lot of progress will be made in research on BWS. It is crucial to frequently review the status of both molecular and clinical aspects of BWS so as to translate these data rapidly. Molecular testing, clinical diagnosis, genetic counseling, and management will all be impacted. In addition, MS-MLPA and modalities of other testing will more correctly reflect the number of BWS cases with recognized molecular lesions, although it is likely that new molecular etiologies recognized for both sporadic cases and familial. Bibliography Benacerraf, B. R. 2007. Ultrasound of fetal syndromes. Philadelphia, Churchill Livingstone / Elsevier. https://books.google.co.ke/books?id=1MHFF0UOKAUC&pg=PA145&dq=Beckwith%E2%80%93Wiedemann+syndrome&hl=en&sa=X&ei=xzQlVYOTJtTnauurgagC&redir_esc=y#v=onepage&q=Beckwith%E2%80%93Wiedemann%20syndrome&f=false Lovell, W. W., Winter, R. B., Morrissy, R. T., & Weintein, S. L. 2006. Lovell and Winters Pediatric orthopaedics. Philadelphia, Lippincott Williams & Wilkins. https://books.google.co.ke/books?id=2ompn48QmG0C&pg=PA267&dq=Beckwith%E2%80%93Wiedemann+syndrome&hl=en&sa=X&ei=xzQlVYOTJtTnauurgagC&redir_esc=y#v=onepage&q=Beckwith%E2%80%93Wiedemann%20syndrome&f=false Eentezami, M., & Knoll, U. 2004. Ultrasound diagnosis of fetal anomalies. 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A. 2010. Principles of Clinical Cancer Genetics a Handbook from the Massachusetts General Hospital. Boston, MA, Springer Science+Business Media, LLC. http://site.ebrary.com/id/10404543. Engel, E., Antonarakis, S. E., Delozier-Blanchet, C. D., & Lyle, R. 2001.Genomic Imprinting and Uniparental Disomy in Medicine Clinical and Molecular Aspects. Hoboken, NJ, John Wiley & Sons. http://www.123library.org/book_details/?id=3876. Walterhouse, D. O. 1997. Diagnostic and therapeutic advances in pediatric oncology. Boston [u.a.], Kluwer. https://books.google.co.ke/books?id=jEydYR8Uz54C&pg=PA34&dq=Beckwith%E2%80%93Wiedemann+syndrome&hl=en&sa=X&ei=XzclVcWLEsTwaIeEgeAL&redir_esc=y#v=onepage&q=Beckwith%E2%80%93Wiedemann%20syndrome&f=false Read More