Adrenal hypoplasia is a rare, life-threatening congenital disorder. Here we define a new form of syndromic adrenal hypoplasia, which we propose to term MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) syndrome. By exome sequencing and follow-up studies, we identified 11 patients with adrenal hypoplasia and common extra-adrenal features harboring mutations in SAMD9. Expression of the wild-type SAMD9 protein, a facilitator of endosome fusion, caused mild growth restriction in cultured cells, whereas expression of mutants caused profound growth inhibition. Patient-derived fibroblasts had restricted growth, decreased plasma membrane EGFR expression, increased size of early endosomes, and intracellular accumulation of giant vesicles carrying a late endosome marker. Of interest, two patients developed myelodysplasitc syndrome (MDS) that was accompanied by loss of the chromosome 7 carrying the SAMD9 mutation. Considering the potent growth-restricting activity of the SAMD9 mutants, the loss of chromosome 7 presumably occurred as an adaptation to the growth-restricting condition.

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Neonatal myocardial infarction is rare and its prognosis is poor. We describe the clinical course and autopsy findings of a newborn female with myocardial infarction. Her clinical course was rapidly progressive, becoming fatal before we could detect the cause. Autopsy demonstrated significant occlusion of the left coronary artery as well as evidence of new infarction, suggesting that the event occurred at birth. This case illustrates myocardial infarction as a possible cause of early neonatal death.

Background: Patent ductus arteriosus (PDA), which disrupts the hemodynamics early after birth, causes intraventricular hemorrhage and neonatal necrotizing. Unlike medical treatment for hemodynamically significant PDA, there are institutional disparities in the criteria for surgical treatment Methods: We aimed to clarify the postoperative indications of surgery for hemodynamically significant PDA and the postoperative complications associated with surgery. Results: Thirty-six extremely-low-birthweight infants (median gestational age 25.2 weeks, median birthweight 699 g) required video-assisted thoracoscopic surgery for PDA (VATS-PDA). The treatment indication of VATS-PDA was resistance to medical treatment in 17 cases, relapsed PDA in 15 cases, and no additional administration of indomethacin because of severe side effects in four cases. Complications with VATS-PDA occurred in eight of 36 cases. There were three cases of pneumothorax, two of thoracotomy transition, two of pulmonary hemorrhage, and four of post-ligation cardiac syndrome (PLCS). VATS-PDA-related death occurred in two cases due to PLCS. The frequency of four or more administrations of indomethacin, with or without postoperative complications, was 88% vs. 39%, respectively (P = 0.04). Conclusions: All postoperative deaths were caused by PLCS, which had the highest risk of poor prognosis. VATS-PDA should be considered for unclosed PDA after one course of indomethacin administration.

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