SUMMARYInfants undergoing open heart surgery often have all or part of their thymus removed. The activity of the immune system has not been investigated thoroughly in these children, and only shortly after the operation. Therefore, it was decided to investigate the activity of the immune system in more detail in children several years after their operation. Peripheral blood samples from 19 children who had undergone open heart surgery during their first months of life was collected (study group) and from 19 ageand gender-matched children (control group). The activity of the immune system was evaluated by measuring the number of different cell types in peripheral blood, the phenotype of lymphocytes and the response of T cells following in vitro stimulation by mitogen, tetanus toxoid and measles antigen. The study group had significantly lower counts of total lymphocytes, which was reflected in a lower number of T cells but not B cells. Furthermore, the study group had significantly lower proportion of T cells (CD3 + ) and helper T cells (CD4 + ), but not cytotoxic T cells (CD8 + ). The level of neutrophils in peripheral blood was significantly higher in the study group. This may indicate enhanced innate immunity when the acquired immunity is defective. The results indicate a shift to extrathymic T cell maturation, which is less efficient for CD4 + helper cells than for CD8 + cytotoxic cells.

Atrial septal defects (ASDs) are found more frequently in the pediatric population than in adults, and improved diagnostic techniques with echocardiography (2DE) and Doppler facilitate diagnosis so that repair is possible at an optimal time. The purpose of our investigation was to study the size of ASDs at diagnosis, how size changes during follow-up, and to explore the relationship between size at diagnosis and need for surgery. We reviewed the medical records of all patients in Iceland with the diagnosis of ASD born between 1984 and 1993. ASD was confirmed by 2DE in all patients and defects smaller than 4 mm were excluded. ASD size was measured by 2DE from subxyphoid long and short axis views. There were 91 patients-29 males and 62 females. Four patients died from causes other than the heart defect and had not been operated upon. Seven patients with ASD primum and sinus venosus defects were excluded from analysis. There were 29 patients with a 4 mm defect, 17 patients with 5 or 6 mm defects, 8 patients with 7 or 8 mm defects, and 26 patients had defects >8 mm. In the 4 mm group, in 26 patients (89%) the ASD closed spontaneously or decreased in size, and 1 patient had been operated upon. In the 5 or 6 mm group, 15 of 19 ASDs (79%) had closed spontaneously, and 2 patients (9.5%) had been operated upon. In the 7 or 8 mm group, 1 of 6 ASDs (16.6%) had closed spontaneously and 3 had been closed surgically. In the >8 mm group, 1 of 24 ASDs had closed spontaneously and 20 (91%) had been closed surgically. We conclude that defects smaller than 6 mm in diameter are very likely to close spontaneously although follow-up is necessary. Defects larger than 8 mm have a high probability requiring operative closure.

AimsCoarctation of the aorta (CoA) accounts for 4–8% of congenital heart defects (CHDs) and confers substantial morbidity despite treatment. It is increasingly recognized as a highly heritable condition. The aim of the study was to search for sequence variants that affect the risk of CoA.Methods and resultsWe performed a genome-wide association study of CoA among Icelanders (120 cases and 355 166 controls) based on imputed variants identified through whole-genome sequencing. We found association with a rare (frequency = 0.34%) missense mutation p.Arg721Trp in MYH6 (odds ratio = 44.2, P = 5.0 × 10−22), encoding the alpha-heavy chain subunit of cardiac myosin, an essential sarcomere protein. Approximately 20% of individuals with CoA in Iceland carry this mutation. We show that p.Arg721Trp also associates with other CHDs, in particular bicuspid aortic valve. We have previously reported broad effects of p.Arg721Trp on cardiac electrical function and strong association with sick sinus syndrome and atrial fibrillation.ConclusionThrough a population approach, we found that a rare missense mutation p.Arg721Trp in the sarcomere gene MYH6 has a strong effect on the risk of CoA and explains a substantial fraction of the Icelanders with CoA. This is the first mutation associated with non-familial or sporadic form of CoA at a population level. The p.Arg721Trp in MYH6 causes a cardiac syndrome with highly variable expressivity and emphasizes the importance of sarcomere integrity for cardiac development and function.

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