Pediatric patients with Down syndrome (DS) are at an increased risk of developing certain cancers. Specifically, patients with DS have a reported 10 – 20 fold increased risk of developing acute myeloid leukemia (AML). Anthracycline-based treatment regimens achieve good results in patients with DS and AML. It has been proposed that DS status constitutes a risk factor for the cardiotoxicity associated with the use of anthracyclines in the pediatric setting. However, published evidence pointing towards an increased risk for cardiotoxicity in patients with DS is relatively scarce and conflictive. This concise review compiles literature relating to the incidence of anthracycline-related cardiotoxicity in pediatric patients with DS. In general, reports from trials using anthracyclines at the maximum recommended dose showed increases in the incidence of anthracycline-related cardiotoxicity in patients with DS in comparison to trials that used anthracyclines at reduced doses. Evidence from the literature suggests that patients with DS can achieve favorable therapeutic outcomes after receiving treatment with reduced doses of anthracyclines to minimize the potential for cardiotoxicity. Further prospective trials, along with the available evidence would assist the design of treatment protocols for patients with pediatric leukemias and DS.

Cancer patients with Down syndrome (DS) are at increased risk for anthracycline-related cardiotoxicity. Mitochondrial DNA (mtDNA) alterations in hearts with- DS may contribute to anthracycline-related cardiotoxicity. Cardiac mtDNA and the mtDNA4977 deletion were quantitated in samples with- (n = 11) and without- DS (n = 31). Samples with- DS showed 30% lower mtDNA (DSMT-ND1/18S ratio: 1.48 ± 0.72 vs. non-DSMT-ND1/18S ratio: 2.10± 1.59; p = 0.647) and 30% higher frequency of the mtDNA4977 deletion (DS% frequency mtDNA4977 deletion: 0.0086 ± 0.0166 vs. non-DS% frequency mtDNA4977 deletion: 0.0066 ± 0.0124, p= 0.514) than samples without- DS. The BACH1 and microRNA-155 (miR-155) genes are located in chromosome 21, and their products have demonstrated roles during oxidative stress. BACH1 and miR-155 expression did not differ in hearts with- and without- DS. An association between BACH1 and miR-155 expression was detected in hearts without- DS, suggesting alterations between BACH1-miR-155 interactions in the DS settings.

Children with Down syndrome (DS) have a 10 – 30 fold increased risk of developing acute myeloid leukemia or acute lymphoblastic leukemia. Patients with DS and leukemia are treated with the same chemotherapeutic agents as patients without DS. Treatment regimens for pediatric leukemia comprise multiple cytotoxic drugs including methotrexate, doxorubicin, vincristine, cytarabine, and etoposide. There have been reports of increased toxicity, as well as altered therapeutic outcomes in pediatric patients with DS and leukemia. This review is focused on the pharmacokinetics of cytotoxic drugs in pediatric patients with leukemia and DS. The available literature suggests that methotrexate and thioguanine display altered pharmacokinetic parameters in pediatric patients with DS. It has been hypothesized that the variable pharmacokinetics of these drugs may contribute to the increased incidence of treatment-related toxicities seen in DS. Data from a small number of studies suggest that the pharmacokinetics of vincristine, etoposide, doxorubicin, and busulfan are similar between patients with and without DS. Definitive conclusions regarding the pharmacokinetics of cytotoxic drugs in pediatric patients with leukemia and DS are difficult to reach due to limitations in the available studies.

Down syndrome (DS, trisomy 21) is the most common survivable aneuploidy. Individuals with DS may experience multiple comorbid health problems including congenital heart defects, endocrine abnormalities, skin and dental problems, seizure disorders, leukemia, dementia, and obesity. These associated conditions may necessitate pharmacotherapeutic management with various drugs. The complex pathobiology of DS may alter drug disposition and drug response in some cases. For example, reports have documented increased rates of adverse drug reactions in patients with DS treated for leukemia and dementia. Intellectual disability resulting from DS may impact adherence to medication regimens. In this review, we highlight literature focused on pharmacotherapy in DS. We discuss reports of altered drug disposition or response in cases with DS, and explore social factors that may impact medication adherence in the DS setting. Enhanced monitoring during drug therapy in individuals with DS is justified based on reports of altered drug disposition, drug response, and other characteristics present in this population.

The cellular environment associated with coronary artery disease (CAD) can lead to mitochondrial DNA (mtDNA) damage. Mitochondrial variants in some copies of mtDNA (heteroplasmy) and mtDNA content are potential genetic biomarkers for CAD-associated disease states. Massively parallel sequencing and qRT-PCR techniques were used to measure heteroplasmic variants and mtDNA content in heart samples from donors with (n = 8) and without (n = 7) documented CAD. Both groups showed increased numbers of heteroplasmic mtDNA variants in the control region (CR) (p < .0010, ANOVA). The donors with CAD displayed a 41.07% increase in heteroplasmic mtDNA variant number in the CR (p = .043), an 87.50% increase in the number of heteroplasmic mtDNA deletions (p = .12), and a 48.76% increase in the number of heteroplasmic mtDNA single nucleotide variants (p = .029). These data suggest potential trends towards higher cardiac mtDNA heteroplasmy levels in heart samples from donors with CAD.