👤 Barbara Faganel Kotnik

Venous thromboembolism (VTE) are rare but potentially life-threatening conditions in children, usually associated with underlying medical conditions. Some children with diagnosed VTE have genetic risk factors for the development of VTE, as well as for recurrent complications. This study reports risk factors for developing VTE in a homogeneous population of children and adolescents. A total of 155 children and adolescents, aged 0-21 years, who were diagnosed with VTE at the University Children's Hospital, UMC Ljubljana, between July 2006 and October 2021, were included. The median age at the time of the VTE diagnosis was 12.0 years (interquartile range: 1-7 years). Associated medical conditions were present in 75.5% of patients, and thrombophilia was diagnosed in 43.2% of patients. Oncological disease accounted for 27.7% of cases, while infections were found to be the most significant acquired risk factor (17.4%), followed by the presence of a central venous catheter (15.5%). Genetic thrombophilia markers were identified in 27.1% of patients, with the highest frequency in adolescents (62.5%). Factor V (FV) Leiden heterozygote was the most common marker (9.6% of patients), followed by elevated factor VIII (FVIII) activity (5.8%) and elevated Lp(a) levels (5.2%). Combined thrombophilia markers were found in 52.2% of patients. In addition to inherited thrombophilia, 83.3% of patients had acquired risk factors. Compared to previously reported prevalence, a lower occurrence of FV Leiden heterozygote, elevated Lp(a) levels, elevated FVIII activity and antiphospholipid syndrome was observed in our population. Show less

Monogenic obesity is a severe, genetically determined disorder that affects up to 1/1000 newborns. Recent reports on potential new therapeutics and innovative clinical approaches have highlighted the need for early identification of individuals with rare genetic variants that can alter the functioning of the leptin-melanocortin signalling pathway, in order to speed up clinical intervention and reduce the risk of chronic complications. Therefore, next-generation DNA sequencing of central genes in the leptin-melanocortin pathway was performed in 1508 children and adolescents with and without obesity, aged 2-19 years. The recruited cohort comprised approximately 5% of the national paediatric population with obesity. The model-estimated effect size of rare variants in the leptin-melanocortin signalling pathway on longitudinal weight gain between carriers and non-carriers was derived. In total, 21 (1.4%) participants had known disease-causing heterozygous variants (DCVs) in the genes under investigation, and 62 (4.1%) participants were carriers of rare variants of unknown clinical significance (VUS). The estimated frequency of potential genetic variants associated with obesity (including rare VUS) ranged between 1/150 (VUS and DCV) and 1/850 (DCV) and differed significantly between participants with and without obesity. On average, the variants identified would result in approximately 7.6 kg (7.0-12.9 kg at the 95th percentile of body weight) (girls) and 8.4 kg (8.2-14.4 kg) (boys) of additional weight gain in carriers at age 18 years compared with subjects without obesity. In conclusion, children with a genetic predisposition to obesity can be promptly identified and may account for more than 6% of obesity cases. Early identification of genetic variants in the Show less

Proopiomelanocortin (POMC) deficiency is an extremely rare inherited autosomal recessive disorder characterized by severe obesity, adrenal insufficiency, skin hypopigmentation, and red hair. It is caused by pathogenic variants in the Show less