Prenatal diagnosis and perinatal clinical course of isolated left-sided innominate artery.

Isolated left-sided innominate artery, a rare congenital anomaly in which the left-sided innominate artery arises from the main pulmonary trunk, is usually diagnosed incidentally in children and adults. Limited reports exist on its prenatal diagnosis, with none comprehensively describing the associated perinatal haemodynamic changes. We report a case of prenatally diagnosed isolated left-sided innominate artery, describing the postnatal clinical course.

Cardiac features of Noonan syndrome in Japanese patients.

BACKGROUND: Cardiovascular disease is one of the most important problems in long-term follow-up for Noonan syndrome. We examined cardiovascular issues and clinical manifestations, with a focus on the cardiovascular disease and prognosis of patients with Noonan syndrome. METHODS: This single-centre study evaluated patients who were clinically and genetically diagnosed with Noonan syndrome. RESULTS: Forty-three patients diagnosed with Noonan syndrome were analysed. The most prevalent responsible mutation was found in PTPN11 (25/43). The second and third most prevalent causative genes were SOS1 (6/43) and RIT1 (5/43), respectively, and 67.4% of genetically diagnosed patients with Noonan syndrome had structural cardiovascular abnormalities. Pulmonary valve stenosis was prevalent in patients with mutations in PTPN11 (8/25), SOS1 (4/6), and RIT1 (4/5). Hypertrophic cardiomyopathy was found in two of three patients with mutations in RAF1. There was no difference in the cardiovascular events or cardiovascular disease prevalence in patients with or without PTPN11 mutations. The proportion of RIT1 mutation-positive patients who underwent intervention due to cardiovascular disease was significantly higher than that of patients with PTPN11 mutations. Patients who underwent any intervention for pulmonary valve stenosis exhibited significantly higher pulmonary flow velocity than patients who did not undergo intervention, when they visited our hospital for the first time. All patients who underwent intervention for pulmonary valve stenosis had a pulmonary flow velocity of more than 3.0 m/s at first visit. CONCLUSIONS: These findings suggest that genetic information can provide a clinical prognosis for cardiovascular disease and may be part of genotype-based follow-up in Noonan syndrome.

A retrospective study of perioperative clinical seizures and epilepsy in children after operation for CHD.

This study investigated the incidence and risk factors of perioperative clinical seizure and epilepsy in children after operation for CHD. We included 777 consecutive children who underwent operation from January 2013 to December 2016 at Kanagawa Children's Medical Center, Kanagawa, Japan. Perinatal, perioperative, and follow-up medical data were collected. Elastic net regression and mediation analysis were performed to investigate risk factors of perioperative clinical seizure and epilepsy. Anatomic CHD classification was performed based on the preoperative echocardiograms; cardiac surgery was evaluated using Risk Adjustment in Congenital Heart Surgery 1. Twenty-three (3.0%) and 15 (1.9%) patients experienced perioperative clinical seizure and epilepsy, respectively. Partial regression coefficient with epilepsy as the objective variable for anatomical CHD classification, Risk Adjustment in Congenital Heart Surgery 1, and the number of surgeries was 0.367, 0.014, and 0.142, respectively. The proportion of indirect effects on epilepsy via perioperative clinical seizure was 22.0, 21.0, and 33.0%, respectively. The 15 patients with epilepsy included eight cases with cerebral infarction, two cases with cerebral haemorrhage, and three cases with hypoxic-ischaemic encephalopathy; white matter integrity was not found. Anatomical complexity of CHD, high-risk cardiac surgery, and multiple cardiac surgeries were identified as potential risk factors for developing epilepsy, with a low rate of indirect involvement via perioperative clinical seizure and a high rate of direct involvement independently of perioperative clinical seizure. Unlike white matter integrity, stroke and hypoxic-ischaemic encephalopathy were identified as potential factors for developing epilepsy.

RAG1 deficiency may present clinically as selective IgA deficiency.

BACKGROUND: Recombination-activating gene (RAG) 1 and 2 deficiency is seen in patients with severe combined immunodeficiency (SCID) and Omenn syndrome. However, the spectrum of the disease has recently expanded to include a milder phenotype. OBJECTIVE: We analyzed a 4-year-old boy who was initially given the diagnosis of selective immunoglobulin A deficiency (SIgAD) based on immunoglobulin serum levels without any opportunistic infections, rashes, hepatosplenomegaly, autoimmunity or granulomas. The patient was found to be infected with varicella zoster; however, the clinical course was not serious. He produced antiviral antibodies. METHODS: We performed lymphocyte phenotyping, quantification of T cell receptor excision circles (TRECs) and kappa deleting recombination excision circles (KRECs), an analysis of target sequences of RAG1 and 2, a whole-genome SNP array, an in vitro V(D)J recombination assay, a spectratype analysis of the CDR3 region and a flow cytometric analysis of the bone marrow. RESULTS: Lymphocyte phenotyping demonstrated that the ratio of CD4+ to CD8+ T cells was inverted and the majority of CD4+T cells expressed CD45RO antigens in addition to the almost complete lack of B cells. Furthermore, both TRECs and KRECs were absent. Targeted DNA sequencing and SNP array revealed that the patient carried a deletion of RAG1 and RAG2 genes on the paternally-derived chromosome 11, and two maternally-derived novel RAG1 missense mutations (E455K, R764H). In vitro analysis of recombination activity showed that both RAG1 mutant proteins had low, but residual function. CONCLUSIONS: The current case further expands the phenotypic spectrum of mild presentations of RAG deficiency, and suggests that TRECs and KRECs are useful markers for detecting hidden severe, as well as mild, cases.

Electrocardiographic Changes with Age in Japanese Patients with Noonan Syndrome.

Little information is available on age-related electrocardiographic changes in patients with Noonan syndrome. This single-center study evaluated the electrocardiograms of patients with Noonan syndrome. We divided the patients (n = 112; electrocardiograms, 256) into four groups according to age: G1 (1 month-1 year), G2 (1-6 years), G3 (6-12 years), and G4 (>12 years). Typical Noonan syndrome-related electrocardiographic features such as left-axis deviation, abnormal Q wave, wide QRS complex, and small R wave in precordial leads were detected. A high percentage of QRS axis abnormalities was found in all groups. Significant differences in right-axis deviation (RAD) were noted among the groups: 56.5% of G1 patients showed RAD compared with 33.3% of G2, 21.1% of G3, and 19.2% of G4 patients. The small R was also significantly different among the groups: 32.6% of G1 patients showed a small R wave compared with 14.9% of G2, 8.5% of G3, and 15.4% of G4 patients. Of the 53 patients with Noonan syndrome aged 1 month to 2 years, 18 had T-positive V1 with a higher prevalence of pulmonary stenosis and cardiac interventions. QRS axis abnormalities, small R in V6, and T-positive V1 could help diagnose Noonan syndrome in infants or young children.

Cardiac Resynchronization Therapy Using Single Site Left Ventricular Pacing in a Tricuspid Atresia Patient With Left Bundle Branch Block.

Cardiac resynchronization therapy (CRT) is typically achieved by pacing both ventricles. However, left ventricular-only pacing has been shown to be noninferior to biventricular pacing in patients with left bundle branch block and normal atrioventricular conduction. However, there is no evidence in favour of CRT with single-site pacing for patients with single-ventricle physiology. In this case, we performed CRT with single-site pacing in a patient with tricuspid atresia and left bundle branch block, enabling successful Fontan completion.

La thérapie de resynchronisation cardiaque (TRC) consiste généralement en une stimulation des deux ventricules. Il a toutefois été montré que la stimulation du ventricule gauche seulement n'est pas inférieure à la stimulation biventriculaire chez les patients présentant un bloc de branche gauche et une conduction auriculoventriculaire normale. Cependant, aucune donnée probante n'appuie la TRC par stimulation d'une seule cavité cardiaque dans le cas d'un cœur univentriculaire. Dans le cas que nous présentons, nous avons eu recours à la TRC par stimulation d'une seule cavité cardiaque chez une patiente présentant une atrésie tricuspidienne et un bloc de branche gauche, ce qui a permis de réaliser l'intervention de Fontan.

[A case of severe systemic juvenile idiopathic arthritis introduced tocilizumab in early phase of the disease].

A 14-year-old boy was admitted in the former hospital with remittent fever, erythematous rash, joint pain, and muscle pain. Antibiotics were ineffectively administered and then, methylprednisolone (mPSL) pulse therapy with methotrexate was introduced under the diagnosis of suspected systemic juvenile idiopathic arthritis (JIA). However, he still had clinical symptoms and signs, and was transferred to our hospital. Re-examination revealed no malignancies including acute leukemia by bone marrow aspiration, no infectious agents by septic work, and no significant increases of antibodies against several viruses including CMV, EBV, HSV, Parvovirus B19, adenovirus, and so forth. FDG-PET demonstrated the accumulation of (18)F-FDG in bone marrows suggesting systemic JIA. Laboratory findings were leukocytosis and granulocytosis, elevated levels of C-reactive protein, D-dimer, ferritin, and interleukin-6. He was finally diagnosed as having severe systemic JIA. Thus, soon after the additional mPSL pulse therapy, tocilizumab (TCZ) was successfully introduced. In conclusion, for systemic JIA patients with severe systemic inflammation, it will be reasonable to introduce tocilizumab earlier than the guideline suggested to reduce side effects of long-term and large amounts of steroids and to protect the transition to macrophage activation syndrome. Further studies will be needed to recommend appropriate timing of tocilizumab introduction.