Vasilis Michalopoulos 2646938 Parental origin of Syndrome Down and genetical and clinical features of acute lymphoblastic leukemia in Syndrome Down. ABSTRACT Syndrome Down (DS) or Trisomy 21 has a huge social and medical cost in human population. The main purpose of the present study is to assess the parental origin of trisomy 21. Subsequently, the stage in which nondisjunction occurs and the role of maternal age and altered genetic recombination events will be observed. Furthermore, Syndrome Down is associated with number of phenotypes including acute leukemia. Thus, the genetical and clinical features of acute lymphoblastic leukemia (ALL) in Down syndrome will be mentioned. INTRODUCTION Syndrome Down (DS) or Trisomy 21 is one of the most serious and important causes of mental disability. Often patients may suffer from other equally serious diseases. Some examples are congenital heart disease (CHD), Alzheimer disease, cancers and especially acute lymphoblastic leukemia (ALL). Patients are very often more likely to suffer from additional diseases. However, recent surveys have led to an increase in the lifetime of an average patient with Syndrome Down (more specifically 55 years of life) (Asim et al. 2015). Syndrome Down is one of the most serious but also frequent chromosomal abnormalities universal. Trisomy 21 is caused during maternal meiotic division where the chromosomal nondisjunction happened and leads to the disease. Mistakes in the meiotic division occur more often in the first maternal meiotic division than the second one (Vraneković et al. 2012). The phenotype results from DS patients are complex of disparities of genes in chromosome 21 (Hsa 21). The genetic nature of the syndrome combined with the size of the Hsa- which is small- has given scientists the last years boldness to understand better the disease and show its character. Some other causes are a Robertsonian translocation or ring chromosome (Asim et al. 2015). As mentioned, patients of Syndrome Down are likely to suffer from additional diseases. The most common of them is the acute lymphoblastic leukemia (ALL) which causes death to the individuals with Trisomy 21. The percentage of ALL disease in the DS patients is quite big because ALL affects 1 in 300 DS patients. In addition, studies make clear that the outcome of patients of Syndrome Down and Acute Lymphoblastic Leukemia (DS-ALL) is inferior to that of non-DS-ALL. This report will assess the parental origin of trisomy 21 and the differences -genetical and clinical- between DS-ALL patients and non-DS-ALL people.
Moreover, will evaluate the maternal age and the altered genetic recombination as risk factors and the relationship between these two. To answer these questions a study with DS patients from Croatian population will be investigated (Vraneković et al. 2012). Finally, a study will be considered to classify and review 128 DS-ALL pediatric diagnoses in the Nordic counties between 1981 and 2010 (Lundin et al. 2014). MAIN BODY First of all, it is well established that in Syndrome Down or Trisomy 21 one of the factors that have a child with the disease is the mother’s age (maternal age). However, modified genetic recombination is an additional risk factor. Thus, the purpose of this paper is to assess the relationship between altered genetic recombination and maternal age as risk factors for the Syndrome Down. Ιn this experiment, there is a collaboration of the largest cities in Croatia. The number of the blood samples which collected from DS patients was 116 and in 76 cases both mother and father were available. In 40 cases, only the maternal samples were obtained. All parents were healthy and so the karyotypes of them were confirmed as normal. In the experiment the parental origin of trisomy 21, the maternal age as a risk Vasilis Michalopoulos 2646938 factor and events of genetic recombination were analyzed. The study confirmed that the phenomenon of advanced maternal ageing as a risk factor was limited to maternally derived trisomy 21 and was associated with both Meiosis I (MI)and Meiosis II (MII). To conclude, the highest proportion of zero genetic recombination events was found in cases with maternal MI derived trisomy 21 (Vraneković et al. 2012). Many of Trisomy 21 patients have increased the risk of developing acute lymphoblastic leukemia (ALL). Although there are differences -genetical and clinical- between DS-ALL patients and non-DS-ALL people and in this section will be mentioned. Initially, this experiment included a total of 128 childhood and adolescents, were diagnosed for 29 years (between 1981 and 2010) in the Nordic countries. Thus, the clinical and genetic characteristics of all DS patients with B-cell precursor (BCP) ALL were compared only with those of non-DS BCP ALL cases of diagnosis at the same time. The results showed, that DS-ALL have less common and abnormal karyotype comparing to non-DS-ALL people. Moreover, the induction failure is more common in DS-ALL patients than non-DS-ALL. This founding was not surprising because it had repeatedly observed. Finally, it has not been proven clearly in DS-ALL previous, that WBC (white blood cell) count was the only factor which associated with patients’ survival. Although, a high WBC count is a deep-rooted risk factor in pediatric non-DS-ALL(Lundin et al. 2014). Thus, it is well understood from the foregoing paragraphs that maternal age is a risk factor for the birth of a child with trisomy 21 and is associated with both MI and MII. In maternal MI, there is the highest probability of zero genetic recombination events to occur. In addition, two differences were found between DS-ALL and non-DS-ALL people. The first one is the presence of an abnormal karyotype and the second one is the incidence of the induction failure. Lastly WBC count proved as a factor associated with survival on DS-ALL patients.
The purpose of this study is to first assess the paternal origin of trisomy 21. This finding was shown for the first experiment as mentioned. So, maternal origin includes the highest percentage of the parental origin with 93% followed by the paternal with 5% and mitotic origin of 2%. DISCUSSION Syndrome Down is a serious and very common disease. It is a chromosomal abnormality and it is well understood, but many theories and experiments advised and began from scientists in order to find better results and improve in phenotype and genotype correlation. Maternal age is the most well-known risk factor as reported for the disease. Thus, parents must be aware of the specific factor in mind before the pregnancy decision. In particular, parents of 34 years of age and above should be very careful. If a family gets a child with trisomy 21, they should be ready for the incidence of acute lymphoblastic leukemia. An additional risk factor is the altered genetic recombination. It is noteworthy, that DS-ALL patients show less often an abnormal karyotype than the non-DS-ALL people. The DS-ALL ‘’normal’’ karyotype has yet another chromosome 21. By contrast, failure of induction is more common in DS-ALL patients than non-DS-ALL. The first experiment provides information about the parental origin of trisomy 21. As was supposed to be less, the origin was paternal and mitotic. Although, some improvements in the first’s study experiment would be done. Thus, the size of the sample, which covers the maternal age allocation, it could be better if it was not so small because it provides information about the parental origin of Down Syndrome. To conclude and make clear most of the parental origin of trisomy 21 is maternal and is over 90 % in a Croatian population. However, Down Syndrome does not have a specific percentage in every human population in the world and there are differences between them.