Expanding ACTA2 genotypes with corresponding phenotypes overlapping with smooth muscle dysfunction syndrome.

Pathogenic variants in ACTA2, encoding smooth muscle α-actin, predispose to thoracic aortic aneurysms and dissections. ACTA2 variants altering arginine 179 predispose to a more severe, multisystemic disease termed smooth muscle dysfunction syndrome (SMDS; OMIM 613834). Vascular complications of SMDS include patent ductus arteriosus (PDA) or aortopulmonary window, early-onset thoracic aortic disease (TAD), moyamoya-like cerebrovascular disease, and primary pulmonary hypertension. Patients also have dysfunction of other smooth muscle-dependent systems, including congenital mydriasis, hypotonic bladder, and gut hypoperistalsis. Here, we describe five patients with novel heterozygous ACTA2 missense variants, p.Arg179Gly, p.Met46Arg, p.Thr204Ile, p.Arg39Cys, and p.Ile66Asn, who have clinical complications that align or overlap with SMDS. Patients with the ACTA2 p.Arg179Gly and p.Thr204Ile variants display classic features of SMDS. The patient with the ACTA2 p.Met46Arg variant exhibits exclusively vascular complications of SMDS, including early-onset TAD, PDA, and moyamoya-like cerebrovascular disease. The patient with the ACTA2 p.Ile66Asn variant has an unusual vascular complication, a large fusiform internal carotid artery aneurysm. The patient with the ACTA2 p.Arg39Cys variant has pulmonary, gastrointestinal, and genitourinary complications of SMDS but no vascular manifestations. Identifying pathogenic ACTA2 variants associated with features of SMDS is critical for aggressive surveillance and management of vascular and nonvascular complications and delineating the molecular pathogenesis of SMDS.

Aortic root dilation in a child with Marfan syndrome and mosaic Turner syndrome.

Patients with a known genetic cause of aortic root dilation usually have a single underlying aetiology, either a single gene defect as in Marfan syndrome or chromosomal anomaly as in Turner syndrome. However, it is possible, although unlikely, for a patient to inherit multiple independent risk factors for aortic root dilation. We describe such a patient, who inherited Marfan syndrome and a very unusual form of mosaic Turner syndrome. Long-term follow-up of this patient may provide insight into the natural history of this unique genetic combination.

A rare cause of vomiting in a 5-year-old girl.

A 5-year-old previously healthy girl presented to the emergency department (ED) with vomiting for 6 days. Her activity level was normal but her parents described progressive exercise intolerance with frequent recreational breaks approximately 2 days prior to presentation. In addition, the child complained of mild abdominal discomfort that began 24 hours prior to her presentation. She had no diarrhea or changes in her diet or oral intake; she had no dysuria or changes in urination. She had no cough, shortness of breath, dizziness, vision changes, falls, or decreased coordination.

An unusual cause of respiratory distress in an infant.

Partial anomalous venous connection (PAPVC) is a congenital cardiovascular defect where one or more (but not all) of the pulmonary veins return anomalously back to the right atrium, either via a direct or indirect connection. It often occurs with other cardiac defects, most commonly a secundum atrial septal defect. Individuals with a large degree of shunting will present with dyspnea, fatigue, and, in some cases, heart failure. Clinical associations and variants of PAPVC include scimitar syndrome, pseudo-scimitar or meandering right pulmonary vein, sinous venosus defects, malposition of the septum primum, and Turner syndrome. The patient in this case, a previously healthy, 6-month-old, full-term male, presented to the emergency department for evaluation of respiratory distress and wheezing. The infant was first seen in his pediatrician's office, where he was noted to be tachypneic and wheezing. He was feeding without difficulty, voiding well, and was active and playful. The patient had passed critical congenital heart disease screening after his birth and prior to discharge, and the family history was negative for any respiratory or cardiac conditions. Cardiac magnetic resonance imaging is becoming the mode of choice for diagnosis of PAPVC. The definitive treatment is surgical correction, but surgery is not indicated in all cases, especially if the patient is asymptomatic and the degree of shunting is small. Patients with isolated PAPVC who undergo surgical correction have good long-term outcomes. In this case, the patient underwent the Warden procedure, which causes an increased risk of superior vena cava stenosis or obstruction to the right atrium. This patient will require lifelong follow-up to assess for new onset pulmonary venous obstruction.

The role of right ventricular function in paediatric idiopathic dilated cardiomyopathy.

INTRODUCTION: The prevalence of right ventricular dysfunction in idiopathic dilated cardiomyopathy is incompletely studied in children. Furthermore, right ventricular function may signal worse outcomes. We evaluated recently published right ventricular function echocardiographic indices in identifying dysfunction in children with idiopathic dilated cardiomyopathy and the impact of right ventricular dysfunction on long-term prognosis. METHODS: A retrospective database review of right ventricular function indices in 30 patients with idiopathic dilated cardiomyopathy was compared with 60 age- and sex-matched controls from January, 2001 until December, 2010. Right ventricular function was assessed by Doppler tissue peak systolic S', early and late diastolic E' and A' waves and isovolumic acceleration at the tricuspid valve annulus; pulsed wave Doppler tricuspid valve inflow E and A waves; right ventricular myocardial performance index; tricuspid annular plane systolic excursion; right ventricular fractional area change. RESULTS: Right ventricular systolic and diastolic function in idiopathic dilated cardiomyopathy was significantly impaired. All measured indices except for isovolumic acceleration and fractional area change were significantly reduced, with a p-value less than 0.05. There was no right ventricular index predictive of death or transplantation. Patients with poor outcome were significantly more likely to need inotropic support (p-value equal to 0.018), be placed on a ventricular assist device (p equal to 0.005), and have a worse left ventricular ejection fraction z-score (p-value equal to 0.002). CONCLUSION: Right ventricular dysfunction is under-recognised in children presenting with idiopathic dilated cardiomyopathy. The need for clinical circulatory support and left ventricular ejection fraction z-score less than minus 8 were primary determinants of outcome, independent of the degree of derangement in right ventricular function.

Streptococcus pneumoniae purulent pericarditis in a neonate.

Purulent bacterial pericarditis is an uncommon infection that manifests during childhood, and in the post-antibiotic era Streptococcus pneumoniae is an unusual cause.We report a case of purulent bacterial pericarditis in a neonate caused by Streptococcus pneumoniae serotype 7F. Although cases of bacterial pericarditis caused by Streptococcus pneumoniae as a causative agent have been reported, their combination in a neonate is unique and this is, to our knowledge, the first case of this combination in the newborn period.

Outpatient pediatric community-acquired methicillin-resistant Staphylococcus aureus: a polymorphous clinical disease.

Community-acquired methicillin-resistant Staphylococcus aureus (CAMRSA) presents numerous diagnostic and therapeutic problems for the outpatient physician, including the appropriate use of antibiotics and proper counseling of families on ways to prevent household spread. Most cases of CAMRSA in children involve soft tissue and skin infection, which is precisely the type of infection most likely to be diagnosed in a dermatology practice. We reviewed 8 pediatric cases of cutaneous CAMRSA that presented over 8 months. The 8 pediatric patients presented with one or more of the following: folliculitis (n=4), abscesses of the groin (n=3), impetiginized atopic dermatitis (AD)(n=2), pustules (n=2), bullous impetigo (n= 1), and nonbullous impetigo (n=1). Three caregivers of these children developed abscesses in exposed areas such as the forearm (n=3) and calf (n=1). The folliculitis cases involved the abdomen, groin and diaper region, buttocks, and inner thighs; the impetiginized AD did not differ from the distribution of the AD. The variety of clinical presentations and the spread in households represent a few of the many facets of CAMRSA in the pediatric dermatology outpatient setting.

A human monoclonal immunoglobulin M reduces bacteremia and inflammation in a mouse model of systemic pneumococcal infection.

Antibody-based approaches to pneumococcal disease may hold promise for immunocompromised patients in whom vaccines are less immunogenic and/or in the context of antimicrobial resistance. Antibody-mediated protection against experimental pneumococcal pneumonia has been shown to depend on immunoregulation, but the relationship between antibody and protection against pneumococcal sepsis and immunoregulation has not been examined. Similarly, the requirement for B and T cells for antibody efficacy is not known. In this study, we determined the efficacy of the human pneumococcal capsular polysaccharide serotype 3-specific antibody, A7 (immunoglobulin M [IgM]), in secretory IgM (sIgM)(-/-), CD4(-/-), CD8(-/-), muMT(-/-), and SCID mice and investigated its effect on cytokine and chemokine expression in sera and spleens from mice with intact cellular immunity. A7 is known to be protective against systemic infection with serotype 3 and to require complement for efficacy. Compared to that of an isotype control antibody, A7 administration prolonged the survival of mice of each immunodeficient strain and was associated with a significant reduction in CFU in blood, lung, and spleen samples and a significantly reduced level of keratinocyte-derived chemokine (KC), interleukin-6 (IL-6), and macrophage inflammatory protein-2 (MIP-2) expression in normal and sIgM(-/-) mice. Studies with mice treated with penicillin revealed similar reductions in CFU and similar levels of IL-6, KC, or MIP-2 expression in A7- and penicillin-treated mice. These findings demonstrate that natural IgM and B and T cells are dispensable for A7-mediated protection against experimental pneumococcal sepsis and suggest that the efficacy of antibody-mediated protection depends on immunomodulation. Taken together, our data extend the association between antibody-mediated protection and immunomodulation to protection against systemic pneumococcal infection and to a clinically important serotype often responsible for pneumococcal sepsis.