Genetic disorders are the leading cause of infant morbidity and mortality. Due to the large number of genetic diseases, molecular and phenotype heterogeneity and often severe course, these diseases remain undiagnosed. In infants with a suspected acute monogenic disease, rapid whole-exome sequencing (R-WES) can be successfully performed. R-WES (singletons) was performed in 18 unrelated infants with a severe and/or progressing disease with the suspicion of genetic origin hospitalized in an Intensive Care Unit (ICU). Blood samples were also collected from the parents. The results from the R-WES were available after 5-14 days. A conclusive genetic diagnosis was obtained in 13 children, corresponding to an overall diagnostic yield of 72.2%. For nine patients, R-WES was used as a first-tier test. Eight patients were diagnosed with inborn errors of metabolism, mainly mitochondrial diseases. In two patients, the disease was possibly caused by variants in genes which so far have not been associated with human disease (NARS1 and DCAF5). R-WES proved to be an effective diagnostic tool for critically ill infants in ICUs suspected of having a genetic disorder. It also should be considered as a first-tier test after precise clinical description. The quickly obtained diagnosis impacts patient’s medical management, and families can receive genetic counseling.

Overgrowth, macrocephaly, accelerated osseous maturation, variable intellectual disability, and characteristic facial features are the main symptoms of Weaver syndrome, a rare condition caused by mutations in EZH2 gene. Recently, in four patients with Weaver-like symptoms without mutations in EZH2 gene, pathogenic variants in EED were described. We present another patient clinically diagnosed with Weaver syndrome in whom WES revealed an EED de novo mutation affecting two neighboring aminoacids, NM_003797.3:c.917_919delinsCGG/p.(Arg306_Asn307delinsThrAsp) located in one allele (in cis). Our observation, together with previous reports suggests that EED gene testing is warranted in patients with the overgrowth syndrome features and suspicion of Weaver syndrome with normal results of EZH2 gene sequencing.

During the winter months of 2020/2021 a wave of multisystem inflammatory syndrome in children (MIS-C) emerged in Poland. We present the results of a nationwide register aiming to capture and characterise MIS-C with a focus on severity determinants. The first MIS-C wave in Poland was notably high, hence our analysis involved 274 children. The group was 62.8% boys, with a median age of 8.8 years. Besides one Asian, all were White. Overall, the disease course was not as severe as in previous reports, however. Pediatric intensive care treatment was required for merely 23 (8.4%) of children, who were older and exhibited a distinguished clinical picture at hospital admission. We have also identified sex-dependent differences; teenage boys more often had cardiac involvement (decreased ejection fraction in 25.9% vs. 14.7%) and fulfilled macrophage activation syndrome definition (31.0% vs. 15.2%). Among all boys, those hospitalized in pediatric intensive care unit were significantly older (median 11.2 vs. 9.1 years). Henceforth, while ethnicity and sex may affect MIS-C phenotype, management protocols might be not universally applicable, and should rather be adjusted to the specific population.

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Despite the growing literature on multisystem inflammatory syndrome in children (MIS-C), the data in European White population is limited. Our aim was to capture MIS-C emergence in Poland (central Europe) and to describe its characteristics with a focus on severity determinants. Patients who met the MIS-C definition (fever, multiorgan failure, inflammation, and proven SARS-CoV-2 infection or contact) were reported retrospectively and prospectively in an online survey. Study definitions fulfilment was automatically evaluated by a dedicated software. For the assessment of univariate relationships, either directed or divided by sex, age, or disease severity, we used the test for two categorical variables and the Kruskal-Wallis test for categorical-continuous variable pairs. The analysis involved 274 children, 62.8% boys, median age 8.8 years. Besides one Asian, all were European White. Merely 23 (8.4%) required paediatric intensive care treatment (PICU). They were older (11.2 vs. 8.4 years), and at hospital admission had higher respiratory rate (30 v. 20/minute), lower systolic blood pressure (89 vs. 100 mmHg), prolonged capillary refill time (40% vs. 11%), and decreased consciousness (22% vs. 5%). Teenage boys had more common cardiac involvement (fraction 25.9% vs. 14.7% ) and macrophage activation syndrome (31.0% vs. 15.2%) than others. Boys were also more often hospitalised in PICU with age (from median 11.2 years to 9.1). The severity of MIS-C is not as uniform as it seemed, ethnicity and sex may affect MIS-C phenotype. Management might not be universally applicable and should rather be adjusted to the specific population.