A Chromosomal Disorder - Trisomy 8 - Essay Example

Trisomy 8 Trisomy is a condition in which there are 3 instances of the affected chromosome instead of the normal 2. It is actually a type of aneuploidy in which there are abnormal number of chromosomes. The most common trisomy is trisomy 21 or Downs syndrome. The rarest is trisomy 8. Very few cases of complete trisomy are delivered because, most cases get aborted during the first trimester of pregnancy itself (Hale and Keane, 2010). Infact most analyses and information about trisomy 8 have been procured from maosaic forms of trisomy 8 which survive. The extent of physical characteristics, prognosis and complications are highly variable. In some individuals, the symptoms are so minimal that physicians fail to suspect the condition and hence do not evaluate (Agrawal and Agrawal, 2011). In others, there are typical characteristics and complications and the individual suffers from morbidity and mortality. In this essay, symptoms of trisomy 8 will be discussed through literature review. Trisomy 8 is a chromosomal disorder in which there are 3 copies of chromosome 8 in every cells of the body of the individual. Infact, chromosome 8 is the largest of all autosomes that have found to be trisomic among infants who are liveborn. The condition is mostly fatal. The disorder can appear with or without mosaicsm. It occurs sporadically and is definitely not hereditary (Agrawal and Agrawal, 2010). More often than not, complete trisomy 8 affects the developing fetus severely and leads to miscarriage. Hence there are very few cases of complete trisomy 8 which are delivered and followed up. On the other hand, mosaic forms of trisomy 8 are less severely affected and are likely to survive (Wisniewska & Mazurek, 2002). There are very few cases of mosaic trisomy 8 that are documented in literature. The condition is very rare. The phenotypic variability is severe. Some cases may be affected mildly and may have only mild dysmorphic changes whereas, others can have severe congenital malformations. The most common clinical characteristics of trisomy 8 are clinodactyly, thick lips, camptodactyly, mental retardation, deep plantar and palmar skin furrows and anomalies of the vertebrae and hip (Hale and Keane, 2010). Phenotypically, the features of trisomy 8 and mosaics forms of Trisomy 8 are the same. However, since the latter is not potentially lethal, more cases of that condition are seen and reported. Many cases may have subtle symptoms and may go undiagnosed. In suspected cases, karyotyping and cell analysis may help establish the diagnosis (Wisniewska & Mazurek, 2002). Typical clinical features which should rise the suspicion or Trisomy 8 in any individual are mental retardation, high-arched palate, forehead that is prominent, dysplastic ears, low set ears, deformed skull, trunk that is slender, decreased mobility of the joints and deep plantar furrows. In the sole, presence of either a deep furrow or longitudinal crease is pathognomonic of the condition (Hale and Keane, 2010). Other than the above mentioned clinical features, patients with trisomy 8 and mosaic forms of Trisomy 8 are at increased risk of developing myelodysplastic syndrome and leukemias. It has been proposed that these occur due to alterations in the stromal function causing proliferation of the progenitor cell and further expansion. Other complications include agenesis of corpus callosum and congenital heart diseases like great vessel anomalies, septal defects and cardiomyopathy. Congenital heart disease occurs in 25 percent of the patients (Wisniewska & Mazurek, 2002). Renal malformations are very common and occur in every 2nd case (Wisniewska & Mazurek, 2002). Common renal anomalies include ureteral reflux, hydronephrosis and cryptorchidism. Some patients may have extrabiliary atresia. this cana ctually happen because of toxoplasma infection during the periconceptional phase (Hale and Keane, 2010). While trisomy 8 mosaicsms are due to mitotic nondisjunction during zygotic development of the early phase, maternal meiotic errors cause miscarriages in trisomy 8 (Hale and Keane, 2010). Trisomy 8 occurs when during mitosis of the zygote phase of fetal development, nondisjunction of chromosome 8 occurs and the affected chromosomal pair does not divide evenly resulting in very few chromosomes in some cells and too many of them in other cells In the mosaic forms, some cells have 2 copies and some others have 3 copies (Davidsson et al, 2013). The type of cells and tissues that are affected is determined by the timing of nondisjunction in the zygote that is developing. There is enough evidence to suggest that mosaic form of trisomy 8 arises because of a mitotic error in the post-zygotic phase and there is no preferential parenteral origin. There are some reports of GSR 8p gene being involved in trisomy 8 (Schochet al, 2006). However no gene expression analyses have been reported in the mosaic form of trisomy 8. It is difficult to ascertain the incidence of trisomy 8 and mosaic forms of trisomy 8. Trisomy 8 is highly lethal and ends up in first trimester abortion. Since not all aborted fetuses are evaluated, the exact incidence is not known. In mosaic forms, since there is high phenotypic variability, again, the prevalence is difficult to be determined (Hale and Keane, 2010). Mosaic form of Trisomy 8 is also known as Warkany syndrome 2. Complete trisomy probably occurs in about 0.8% of spontaneous pregnancy losses. The estimated frequency of the mosaic form is about 1:5000 to 1:50000 births (Agrawal and Agrawal, 2011). Trisomy 8 is more common in males than in females with the ratio being 5:1 (Agrawal and Agrawal, 2011). Differential diagnosis for Trisomy 8 include arthrogryposis, Fongs syndrome and oto-palato-digital syndrome (Hale and Keane, 2010). Antenatally, diagnosis is possible by analysing chorionic villus sampling. However, this is not always confirmatory because mosaicism in the placenta may be only isolated and does not definitely indicate fetal mosaicsm. Another indicator of trisomy 8 is maternal alpha fetoprotein which is markedly elevated in the condition. Normal fetal blood sampling and normal amniocentesis do not rule out the trisomy 18 in the fetus. It is very difficult to establish clinical diagnosis of trisomy 8 because of subtle clinical characteristics. Confirmatory test after delivery can be done using karyotyping and fibroblast culture of the skin cells (Agrawal and Agrawal, 2011). Trisomy 8 cannot be cured. Ideally, it cannot be prevented because; the cases are sporadic and exact cause is yet unknown. Also antenatal diagnosis is not much reliable. Treatment and medical assistance can be provided based on the complications that arise. To conclude, it can be said that trisomy 8 cases are rarely reported and mosaic cases are more common. The phenotypic characteristics are variable and high degree of suspicion is essential to establish diagnosisis mild cases. References Agrawal, A., and Agrawal, R. (2011). Warkany Syndrome: A Rare Case Report. Case Reports in Pediatrics. Retrieved on 14th April, 2014 from http://dx.doi.org/10.1155/2011/437101 Davidsson, J., Veerla, S., Johansson, B. (2013). Constitutional trisomy 8 mosaicism as a model for epigenetic studies of aneuploidy. Epigenetics & Chromatin, 6:18. Hale, N.E., Keane, J.F. (2010). Piecing Together a Picture of Trisomy 8 Mosaicism Syndrome. The Journal of the American Osteopathic Association, 110(1), 21-23. Schoch, C., Kohlmann, A., Dugas, M., Kern, W., Schnittger, S., Haferlach, T. (2006). Impact of trisomy 8 on expression of genes located on chromosome 8 in different AML subgroups. Genes Chromosomes Cancer, 45, 1164-1168. . Wisniewska, M. & Mazurek, M. (2002). Trisomy 8 mosaicism syndrome. Journal Applied Genetics, 43(1), 115-118. Read More