Kawasaki disease is a systemic vasculitis of unknown etiology, with clinical observations suggesting a substantial genetic contribution to disease susceptibility. We conducted a genome-wide association study and replication analysis in 2,173 individuals with Kawasaki disease and 9,383 controls from five independent sample collections. Two loci exceeded the formal threshold for genome-wide significance. The first locus is a functional polymorphism in the IgG receptor gene FCGR2A (encoding an H131R substitution) (rs1801274; P = 7.35 × 10(-11), odds ratio (OR) = 1.32), with the A allele (coding for histadine) conferring elevated disease risk. The second locus is at 19q13, (P = 2.51 × 10(-9), OR = 1.42 for the rs2233152 SNP near MIA and RAB4B; P = 1.68 × 10(-12), OR = 1.52 for rs28493229 in ITPKC), which confirms previous findings(1). The involvement of the FCGR2A locus may have implications for understanding immune activation in Kawasaki disease pathogenesis and the mechanism of response to intravenous immunoglobulin, the only proven therapy for this disease.
To find new candidate loci predisposing individuals to Kawasaki disease, an acute vasculitis that affects children, we conducted a genome-wide association study in 622 individuals with Kawasaki disease (cases) and 1,107 controls in a Han Chinese population residing in Taiwan, with replication in an independent Han Chinese sample of 261 cases and 550 controls. We report two new loci, one at BLK (encoding B-lymphoid tyrosine kinase) and one at CD40, that are associated with Kawasaki disease at genome-wide significance (P < 5 × 10(-8)). Our findings may lead to a better understanding of the role of immune activation and inflammation in Kawasaki disease pathogenesis.
Infants younger than 6 months with prolonged unexplained febrile illnesses should be suspected as having Kawasaki disease, despite the incomplete clinical presentation. Because early diagnosis and timely treatment are difficult in younger infants with Kawasaki disease because of delayed and incomplete clinical presentations, echocardiogram becomes an important implement for diagnosis. Early intravenous immunoglobulin treatment is required in view of the highest risk of coronary involvement in them.
Tourette syndrome (TS) is a common neuropsychiatric disorder in children characterized by multiple motor and vocal tics that fluctuate in severity and lasting for at least 1 year. Boys are more commonly affected than girls. Symptoms usually begin with simple motor or vocal tics which then evolve into more complex motor and vocal tics over time. Premonitory sensory urges are common in children over the age of 8 years, and these urges help distinguish tics from symptoms of other movement disorders. Common comorbidities of TS include attention deficit hyperactivity disorder, obsessive-compulsive disorder and learning difficulties. Several genes have been assessed as candidate genes for TS; environmental factors such as stress and streptococcal infections might also contribute to its etiology. The pathophysiology of TS mainly involves dysfunction of basal ganglia-related circuits and hyperactive dopaminergic innervations. A thorough history assessment and neurological examination are important for the correct diagnosis and differentiation from other movement disorders. Treatment for TS should focus on improving the patient's social functioning, minimizing the impairment from cormobid disorders, and controlling tics, if they are severe. Commonly used medications for TS include a2-adrenergic agonists and atypical neuroleptics. Habit reversal therapy is an effective option for TS, and repetitive transcranial magnetic stimulation may be a promising approach for severe cases.
Background: Epidemics of enterovirus 71 infection have caused the death of many children throughout the world. Rhombencephalitis, brain stem encephalitis, and heart failure were present in all of the fatal cases. However, no evidence of myocarditis was noted in the heart specimens, and the mechanism of heart failure remains unknown. Aims: To characterise the presentation of cardiac complications in children with enterovirus rhombencephalitis and discuss its pathogenesis. Methods: Ninety one consecutive patients with enterovirus rhombencephalitis underwent echocardiography. Of these, 17 patients (nine male, eight female; median age 14 months, range 4-57 months) with left ventricular dysfunction were studied. Results: Tachycardia was noted in all patients and systemic hypertension in 12. Muscle-brain fraction of creatine kinase was .5% in 14 patients. Plasma norepinephrine and epinephrine levels were significantly raised in the three patients in whom these were analysed. Electrocardiographic abnormalities were noted in eight patients. Pulmonary oedema was complicated in 15 patients. The initial ejection fraction of the left ventricle was 22-58% (mean 37%, SD 11%). All patients deteriorated to hypotensive shock within 12 hours and 13 died. Heart specimens from seven patients showed no evidence of myocarditis, but significant coagulative myocytolysis, myofibrillar degeneration, and cardiomyocyte apoptosis were observed. Conclusions: Acute heart failure was noted in 19% of patients with enterovirus rhombencephalitis, which had a fatality rate of 77%. It was not caused by myocarditis but possibly by neurogenic cardiac damage.
The mortality rate of patients with retinoblastoma is higher in Taiwan than in developed countries. The proportion of patients' parents refusing or delaying treatment in Taiwan is high. The factors for a poor prognosis were an interval between onset and treatment of >5 months, a lag time before treatment of >2.5 months, and extraocular disease. The duration of symptoms was not a prognostic factor. The only independent factor indicating a poor prognosis was extraocular disease.
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