Because Cardio-facio-cutaneous (CFC) syndrome has significant phenotypic overlap with Costello syndrome, it may be difficult to establish the diagnosis on a clinical basis. The recent discoveries of germline HRAS mutations in patients with Costello syndrome and mutations in BRAF, MEK1, and MEK2 in CFC syndrome uncovered the biologic mechanism for the shared phenotypic findings based on the close interaction of the affected gene products within the MAP kinase pathway. We evaluated a series of patients who were either clinically diagnosed with Costello syndrome, or in whom the diagnoses of both Costello and CFC syndromes were considered. After excluding mutations in HRAS, we identified eight changes in BRAF and five in MEK1. Five mutations are novel, and all changes occurred de novo among those triads tested. A review of the clinical abnormalities showed important differences between patients with either a BRAF or MEK1 mutation, and those previously reported with an HRAS mutation. Statistical significance was achieved, despite the relatively small number of patients with BRAF and MEK1 mutations reported here, for polyhydramnios, growth hormone deficiency and the presence of more than one papilloma, which were less common in CFC compared to HRAS mutation positive patients. Although both CFC and Costello syndrome are characterized by cardiac abnormalities in about three-fourths of patients, the pattern of congenital heart defects (CHD), hypertrophic cardiomyopathy (HCM), and tachycardia differs somewhat. CHD, especially pulmonic stenosis associated with a secundum-type atrial septal defect, are more common in CFC than Costello syndrome (P = 0.02). Atrial tachycardia is less frequent in CFC patients with BRAF or MEK1 mutations, compared to Costello syndrome patients with HRAS mutation (P = 0.04). Chaotic atrial rhythm or multifocal atrial tachycardia was observed only in Costello syndrome. Malignant tumors have been viewed as characteristic for Costello syndrome due to HRAS mutations, however, we report here on a MEK1 mutation in a patient with a malignant tumor, a hepatoblastoma. Although this indicates that the presence of a tumor is not specific for Costello syndrome with HRAS mutation, it is noteworthy that the tumor histology differs from those commonly seen in Costello syndrome. Based on these clinical differences we suggest that patients with BRAF and MEK mutations should be diagnosed with CFC syndrome, and the diagnosis of Costello syndrome be reserved for patients with HRAS mutations.

Cardiomyopathy associated with HIV-1 infection is a well-recognized complication. However, it is unknown whether direct cardiomyocyte infection is involved in the pathogenesis of the cardiomyopathy. An HIV-1-based lentiviral vector and wild-type HIV-1 were used to infect human fetal cardiac myocytes in a primary culture. Quantitative polymerase chain reaction, viral p24 antigen determination, and immunofluorescence were used to detect the synthesis of HIV-1 DNA and proteins after the infection. High-efficiency infection occurred using the HIV-1-based lentiviral vector, although no infection occurred with the wild-type HIV-1 strain. Dual-labeling immunofluorescence for HIV-1 proteins and myosin confirmed that cardiomyocytes were infected. This in vitro analysis suggests that direct myocyte infection with wild-type HIV-1 may not be involved in the pathogenesis of HIV-1 cardiomyopathy. However, HIV-1-based vectors may prove useful for ex vivo cardiovascular gene therapy.

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FIG. 1 Chest x-ray. The right pulmonary artery (RPA) and pulmonary trunk (PT) are aneurysmal. Arrow identities a much less dilated left pulmonary artery. In his 1958 landmark article that defined the Eisenmenger syndrome, Paul Wood observed, "Dilatation of the right branch of the pulmonary artery was remarkable in only 6% of cases with ventricular septal defect,''' a radiologic observation that has withstood the test of time. We call attention to a dramatic exception in a 52-year-old male. The posteroanterior chest x-ray (Fig. 1) shows aneurysmal dilatation of the right pulmonary artery (MA) and the pulmonary trunk (PT).

Background: Pediatric cardiac surgery in developing countries poses many challenges. The practice of referring patients from abroad via nongovernmental organizations has occurred for many years. We describe our experience with international referrals for pediatric cardiac surgery via Gift of Life Mid-South to the Heart Institute, Le Bonheur Children’s Hospital in Memphis, Tennessee. Methods: We performed a retrospective descriptive review of data collected in our Society of Thoracic Surgeons Congenital Heart Surgery Database (STS CHSD) along with data from our electronic medical record from January 1, 2007, to December 31, 2017. Available data included patient demographics, diagnoses, surgical procedure, entire inpatient length of stay (LOS), complications, and operative mortality. Cardiac surgeries were grouped according to the Society of Thoracic Surgeons–European Association for Cardio-Thoracic Surgery Congenital Heart Surgery Mortality Categories (STAT Mortality Categories). Complications were defined according to the STS CHSD. Results: In this retrospective descriptive study, case complexity level varied; however, 38% cardiac surgeries were in STAT Mortality Category 3 or 4. Honduras was the most common referral source with a total of 18 countries represented. Operative mortality remained very low (1 [1.4%] of 71 cardiac surgeries) despite patients being referred beyond infancy. There were an increasing number of complications and longer inpatient LOS (with greater variance) in STAT Mortality Category 4. Conclusions: International patients referred for congenital heart surgery can be successfully treated with an acceptable mortality rate despite late referrals. Inpatient LOS is related to surgical complexity. Follow-up studies are needed to determine the long-term outcomes of these patients.