Genetic evaluation of newborns with critical congenital heart defects admitted to the intensive care unit.

Rapid and efficient diagnostics is crucial for newborns with congenital heart defects (CHD) in intensive care unit (ICU) but is often challenging. Given that genetic factors play a role in 20-30% cases of CHD, it is likely that genetic tests could improve both its speed and efficiency. We aimed to analyze the utility of rapid and cost-effective multiplex ligation dependent probe amplification analysis (MLPA) for chromosomal analysis in newborns with critical CHD. One hundred consecutive newborns admitted with critical CHD to the ICU were included in the study. Those with normal MLPA findings were further tested by chromosomal microarray and clinical exome sequencing. Overall, pathogenic/likely pathogenic variants were determined in ten (10%) newborns by MLPA, three (3%) by chromosomal microarray, and three (3%) by clinical exome sequencing. The most common variant detected was deletion of 22q11.2 region.Conclusion: MLPA is fast and cost-effective analysis that could be used as the first-tier test in newborns with critical CHD admitted to the ICU. What is Known: • MLPA is an established method for chromosome analysis in patients with CHD, but detection rate in newborns with critical CHD is unknown. What is New: • Study suggests that detection rate of casual variants using MLPA in newborns with critical CHD is 10%.

Diagnostic and Clinical Utility of Clinical Exome Sequencing in Children With Moderate and Severe Global Developmental Delay / Intellectual Disability.

Clinical exome sequencing is currently being used in diagnostics of various genetic disorders, but studies supporting its application in clinical setting are scarce. The aim of this study was to establish diagnostic and clinical utility of clinical exome sequencing in patients with moderate and severe global developmental delay/intellectual disability. Clinical diagnosis was made in 49 of 88 investigated patients, with overall diagnostic yield of 55.7%. Molecular findings are characterized in detail, including the impact of newly made diagnosis on clinical management. Several previously unreported genotype-phenotype correlations and 33 novel variants are described. Genetic and clinical data were shared through publicly available database. In conclusion, clinical exome sequencing allows identification of causative variants in a significant proportion of patients in investigated clinical subgroup. Compared to whole exome sequencing, it shows similar diagnostic and clinical utility with reduced costs, which could be of particular importance for institutions with limited resources.

The Impact of 22q11.2 Microdeletion on Cardiac Surgery Postoperative Outcome.

22q11.2 microdeletion is the most common microdeletion in humans. The purpose of this study was to evaluate postoperative outcome in children with 22q11.2 microdeletion who had undergone complete surgical correction of a congenital heart defect. The study included 34 patients who underwent complete correction of conotruncal heart defects. Of these, 17 patients diagnosed with 22q11.2 microdeletion represent the investigated group. Another 17 patients without 22q11.2 microdeletion represent the control group. Investigated and control groups differ significantly for total length of stay in the hospital (average 37.35 and 14.12 days, respectively); length of postoperative stay in the intensive care unit (average 10.82 and 6.76 days, respectively); sepsis (eight and two patients, respectively); administration of antibiotics (15 and seven patients, respectively); duration of antibiotic therapy (average 17.65 and 14.59 days, respectively); occurrence of hypocalcemia (16 and 0 patients, respectively); and initiation of peroral nutrition during the postoperative course (average 10.29 and 3.88 days, respectively). No difference was found for duration of ventilatory support (average 6.12 and 4.24 days, respectively), administration of total parenteral nutrition, and postoperative mortality rate. The study results suggest that genotype of 22q11.2 microdeletion affects postoperative outcome after cardiac surgery. Possible targets for intervention in postoperative intensive care management are prevention and treatment of systemic infections, monitoring, and treatment of hypocalcemias, rational administration of antibiotics and careful planning of nutrition. Consequently, this could shorten patients' intensive care stay and overall duration of hospitalization.

Improving the Diagnosis of Children with 22q11.2 Deletion Syndrome: A Single-center Experience from Serbia.

OBJECTIVE: The incidence of the 22q11.2 microdeletion among children who have at least two out of five major clinical criteria for 22q11.2 deletion syndrome. DESIGN: Prospective study. SETTING: University Childrens Hospital in Belgrade, Serbia between 2005 and 2014. PARTICIPANTS: 57 patients with clinical characteristics of 22q11.2 deletion syndrome. METHODS: Standard G-banding cytogenetic analysis was performed in all children, and the 22q11.2 genomic region was examined using fluorescence in situ hybridization (FISH). For patients with no deletion detected by FISH, multiplex ligation-dependent probe amplification (MLPA) analysis was also done in order to detect cryptic deletions of this region and to analyze other genomic loci associated with phenotypes resembling the syndrome. A selected group of patients diagnosed to have 22q11.2 microdeletion by FISH underwent MLPA testing in order to characterize the size and position of deletion. OUTCOME MEASURES: The frequency of 22q11.2 microdeletion among children with at least two of the five major characteristics of 22q11.2 deletion syndrome (heart malformations, facial dysmorphism, T-cell immunodeficiency, palatal clefts and hypocalcemia/hypoparathyroidism). RESULTS: Typical 22q11.2 microdeletion was detected in 42.1% of patients; heart malformation were identified in all of them, facial dysmorphism in 79.2%, immunological problems in 63.6%, hypocalcemia in 62.5% and cleft palate in 8.3%. CONCLUSION: A higher detection rate compared to one-feature criterion is obtained when at least two major features of 22q11.2 deletion syndrome are taking into consideration. The criteria applied in this study could be considered by centers in low-income countries.

Clients' Perception of Outcome of Team-Based Prenatal and Reproductive Genetic Counseling in Serbian Service Using the Perceived Personal Control (PPC) Questionnaire.

This is the first study in Serbia and the region of South-East Europe dedicated to clients' perception of outcome and efficiency of prenatal and reproductive genetic counseling. The primary aim of this study was to assess overall value and success of genetic counseling in prenatal and reproductive care with regard to perceived personal control of clients, reflecting also in a part patient comprehension, knowledge retention, and empowerment in decision-making. The standardized Perceived Personal Control questionnaire (PPC) was used for the assessment of 239 female participants. First, we performed a complete validation of the psychometric characteristics of the Serbian-language version of the PPC questionnaire. The validation of the questionnaire permits other researchers from Serbian-speaking regions of South-East Europe to use this standard instrument to assess the effectiveness of prenatal genetic counseling in their communities and analyze advantages and disadvantages of their counseling models. We also measured social and demographic characteristics of participants. Further, we analyzed effects of our team-based prenatal and reproductive genetic counseling model through (a) calculation of PPC scores at three different stages (before initial, after initial, and before second counseling session), and (b) by assessing participants' responses by indication for referral (advanced maternal age, abnormal biochemical screening, family history of hereditary disorders, maternal exposure to drugs, exposure to radiation, exposure to infective agents, infertility or recurrent abortions, and miscellaneous). The results indicate that participants' knowledge after initial counseling increased significantly and after that remained stable and sustainable. A satisfactory level of confidence among participants had been achieved, in that many felt an increased sense of control over their situation and emotional response to it. Indirectly, these results indicate the success of a team-based prenatal genetic counseling model, which has not been assessed in the literature to date.