Exome sequencing implicates ancestry-related Mendelian variation at SYNE1 in childhood-onset essential hypertension.

Childhood-onset essential hypertension (COEH) is an uncommon form of hypertension that manifests in childhood or adolescence and, in the United States, disproportionately affects children of African ancestry. The etiology of COEH is unknown, but its childhood onset, low prevalence, high heritability, and skewed ancestral demography suggest the potential to identify rare genetic variation segregating in a Mendelian manner among affected individuals and thereby implicate genes important to disease pathogenesis. However, no COEH genes have been reported to date. Here, we identify recessive segregation of rare and putatively damaging missense variation in the spectrin domain of spectrin repeat containing nuclear envelope protein 1 (SYNE1), a cardiovascular candidate gene, in 3 of 16 families with early-onset COEH without an antecedent family history. By leveraging exome sequence data from an additional 48 COEH families, 1,700 in-house trios, and publicly available data sets, we demonstrate that compound heterozygous SYNE1 variation in these COEH individuals occurred more often than expected by chance and that this class of biallelic rare variation was significantly enriched among individuals of African genetic ancestry. Using in vitro shRNA knockdown of SYNE1, we show that reduced SYNE1 expression resulted in a substantial decrease in the elasticity of smooth muscle vascular cells that could be rescued by pharmacological inhibition of the downstream RhoA/Rho-associated protein kinase pathway. These results provide insights into the molecular genetics and underlying pathophysiology of COEH and suggest a role for precision therapeutics in the future.

Point-of-Care Ultrasound in Sternal Notch Confirms Depth of Endotracheal Tube in Children.

OBJECTIVES: To determine if a saline-filled cuff seen at the suprasternal notch on ultrasound corresponds to correct endotracheal tube depth on a chest radiograph (tip at/below clavicle AND ≥ 1 cm above carina). DESIGN: Prospective observational study. SETTING: Tertiary Care Pediatric hospital. PATIENTS: Patients between the ages of 0-18 years requiring nonemergent cardiac catheterizations and endotracheal intubation with a cuffed endotracheal tube were included in the study. Children with anticipated or known difficult airways were excluded. INTERVENTIONS: Ultrasound evaluation of the neck following saline inflation of the endotracheal tube cuff. MEASUREMENTS AND MAIN RESULTS: Ultrasonography of the patient's neck was performed following intubation by a pediatric anesthesiologist. A linear probe was used in transverse axis to identify the saline-filled cuff starting at the suprasternal notch and moving cephalad. A cine-fluoroscopic image, similar to a chest radiograph, was obtained to ascertain the endotracheal tube depth after the cuff was identified sonographically. Endotracheal tube cuffs seen on ultrasound at the suprasternal notch were compared with the endotracheal tube depth on the cine-fluoroscopic image. A total of 75 children were enrolled in the study. The endotracheal tube was seen sonographically at the suprasternal notch in 70 patients of which 60 had complete data (an adequate chest radiograph available for review). Patient ages ranged from 2 months to 18 years with a median age of 4 years. The median endotracheal tube tip to carina distance was 2.4 cm (interquartile range, 1.75-3.3 cm.) The endotracheal tube tip to carina distance was greater than or equal to 1 cm in 57 out of the 60 patients. Endotracheal tube cuff at the suprasternal notch on ultrasound corresponded with correct endotracheal tube depth on chest radiograph with an accuracy of 95% (CI, 86-98%). CONCLUSIONS: Visualization of the cuff at the suprasternal notch by ultrasound demonstrates potential as a means of confirming correct depth of the endotracheal tube following endotracheal intubation.

A Primer on Multimodal Imaging and Cardiology-Radiology Congenital Heart Interface.

Pediatric cardiology imaging laboratories in the present day have several modalities for imaging of congenital and acquired cardiovascular disease. These modalities include echocardiography, cardiovascular magnetic resonance imaging, cardiac computed tomography and nuclear imaging. The utility and limitations of multimodal imaging is described herein along with a framework for establishing a cardiology-radiology interface.

Epidemiology of Childhood Onset Essential Hypertension.

The knowledge of epidemiology of a disease is paramount in identifying preventive measures. Currently there is a paucity of literature on the epidemiologic determinants of childhood onset essential hypertension (EH). We evaluated children with EH, ascertained in a rigorous manner, in a large multiethnic population in a tertiary pediatric hypertension clinic. We enrolled children with and without EH and obtained data by in-person interview of their parents and by direct anthropometric measurements including blood pressures. A total of 148 children (76 hypertension probands, 72 control probands, and males 53%, mean age 12.2 ± 4.3 years) were enrolled. Of these 148 children, 51 pairs were matched 1:1 on ethnicity, gender and age (±2.5 years). In this study we evaluated the demographics, genetic predisposition and a variety of exposures including, socioeconomic, perinatal, lifestyle and environmental, between cases and controls. All measures were similar between cases and controls other than a significantly higher BMI (p = 0.01) and rates of obesity (p = 0.03), and a difference of near-significance in any family history of EH (p = 0.05) higher in cases compared to controls. The odds of obesity was 3.5 times higher among cases than controls. In this study, we evaluated a variety of prenatal and postnatal exposures that could potentially contributed to the EH phenotype in childhood. The findings of the study elucidate the epidemiology of EH in children and two important associated risk factors, any family history of hypertension and a higher body weight.

Familial aggregation of first degree relatives of children with essential hypertension.

PURPOSE: Determining familial aggregation is an important first step in narrowing the search for disease-causing genes and hence we determined the familial aggregation of EH among first degree relatives of children with EH. MATERIALS AND METHODS: We prospectively enrolled children with EH along with their first degree relatives from a tertiary pediatric hypertension clinic in a large ambulatory care center. We utilized rigorous methodology for blood pressure (BP) measurements and diagnoses of EH to reduce the heterogeneity in the phenotype. For those enrolled, parental BP status was confirmed by in-clinic direct BP measurements. We also enrolled control children without EH along with their first degree relatives from the same pediatric ambulatory center. RESULTS: In our case-control study of 153 families, the odds of having familial EH was more than 3 times higher among the cases than in controls (OR: 3.63, 95% CI: 1.85-7.12) with 71% of the cases and 41% of the controls reporting familial EH. One parent with EH was seen in 88% of the cases and 52% of the controls (OR: 6.92, 95% CI: 2.68-17.84). The odds of at least one parent (compared to neither) with EH was almost 7-fold higher, and odds of having two parents with EH was 14-fold higher among cases versus controls. The risk of EH did not go back from the first degree relative to the second degree relatives. CONCLUSIONS: We identified familial aggregation with an increased liability of childhood onset EH with parental EH. The risk of childhood onset EH is more than doubled in the presence of EH in both parents versus in a single parent. Prediction for childhood-onset EH is improved by obtaining a family history of EH in the first degree relatives.

Whole-exome sequencing reveals an inherited R566X mutation of the epithelial sodium channel ß-subunit in a case of early-onset phenotype of Liddle syndrome.

To comprehensively evaluate a European-American child with severe hypertension, whole-exome sequencing (WES) was performed on the child and parents, which identified causal variation of the proband's early-onset disease. The proband's hypertension was resistant to treatment, requiring a multiple drug regimen including amiloride, spironolactone, and hydrochlorothiazide. We suspected a monogenic form of hypertension because of the persistent hypokalemia with low plasma levels of renin and aldosterone. To address this, we focused on rare functional variants and indels, and performed gene-based tests incorporating linkage scores and allele frequency and filtered on deleterious functional mutations. Drawing upon clinical presentation, 27 genes were selected evidenced to cause monogenic hypertension and matched to the gene-based results. This resulted in the identification of a stop-gain mutation in an epithelial sodium channel (ENaC), SCNN1B, an established Liddle syndrome gene, shared by the child and her father. Interestingly, the father also harbored a missense mutation (p.Trp552Arg) in the α-subunit of the ENaC trimer, SCNN1A, possibly pointing to pseudohypoaldosteronism type I. This case is unique in that we present the early-onset disease and treatment response caused by a canonical stop-gain mutation (p.Arg566*) as well as ENaC digenic hits in the father, emphasizing the utility of WES informing precision medicine.

Blood pressure percentile charts to identify high or low blood pressure in children.

BACKGROUND: The goal was to develop familiar blood pressure (BP) charts representing BP percentile curves similar to CDC growth charts to improve screening of both high and low BP in children. METHODS: Since height accounts for substantially more BP variability than age and is a more direct measure of body size and maturation in children, height-specific BP percentile curves were drawn separately for males and females. We used the 2004 Fourth Report data source and equations to calculate the BP threshold value for each gender and 5 cm height group. By slightly underestimating a child's BP percentile for high BP and slightly overestimating a child's BP percentile for low BP, these charts guarantee 100 % sensitivity in detecting abnormal BP. Sensitivity and specificity of the chart cut-offs were confirmed in a sample of 1254 healthy children from a school-based blood pressure screening program. RESULTS: The 1st, 5th, 25th, 50th, 75th, 90th, 95th, and 99th BP percentile curves are depicted in the chart for each corresponding gender and height from 85 to 190 cm, mimicking the ubiquitous CDC "growth charts". Shaded areas of the chart differentiate abnormal BP status categories: hypotension, normal BP, prehypertension, Stage 1 hypertension, and Stage 2 hypertension. Sensitivity was confirmed to be 100 % with specificity above 94 %. CONCLUSIONS: These simplified BP charts improve upon currently available BP screening reference with the following features: (a) tracking BP longitudinally in an individual child, (b) full physiological range of BP percentiles represented in percentile curve format for rapid identification both high and low BP,

Left Ventricular Hypertrophy Phenotype in Childhood-Onset Essential Hypertension.

The aim of this study was to determine the risk factors associated with left ventricular (LV) hypertrophy (LVH) among 89 untreated children with primary hypertension. Clinic hypertension was confirmed by 24-hour ambulatory blood pressure (BP) monitoring. LV mass (LVM) index was calculated as LVM (g)/height (m)(2.7) and LVH was defined as LVM index >95th percentile. Children with (n=32) and without (n=57) LVH were compared. Both obesity and systolic BP were independently associated with LVH, with a higher contribution by body mass index. Obesity contributed significantly, with a nearly nine-fold increased risk of LVH. There was evidence of effect modification by the presence or absence of obesity on the relationship between systolic BP and LVH, whereby the relationship existed mainly in nonobese rather than obese children. Hence, to achieve reversal of LVH, clinicians should take into account both BP control and weight management.

Myocardial Performance Index in Childhood Onset Essential Hypertension and White Coat Hypertension.

BACKGROUND: As a global measure of ventricular systolic and diastolic function, the myocardial performance index (MPI) can be an early indicator of hypertensive cardiomyopathy in children with essential hypertension (EH). METHODS: Children with untreated newly diagnosed EH and white coat hypertension (WCH) by a 24-hour ambulatory blood pressure monitoring (ABPM), both groups without any identifiable etiology for the hypertension, were enrolled for the study. Echocardiograms and vascular ultrasounds for carotid artery intimal medial thickness were performed on all children prior to therapy. Diastolic function (peak E and A velocities, E/A ratio, isovolumic relaxation time, and deceleration times) and MPI were evaluated by simultaneous transmitral and transaortic spectral Doppler flow velocities. Systolic function was evaluated by shortening fraction and ejection fraction. RESULTS: A cohort of 66 children (24 with EH, 42 with WCH, males 61%, median age of 13 years, range 10-17 years) were enrolled in the study. The demographic, anthropometric, laboratory tests, vascular ultrasound, and conventional echocardiographic parameters were similar between the 2 groups. There was a very small difference in MPI between the EH and WCH children (0.28 SD: 0.07 vs. 0.31 SD: 0.08, P = 0.045). However, in EH children, MPI increased by 0.14 units for every 10 unit increase in mean ABPM systolic BP (95% confidence interval: 0.03-0.25). CONCLUSIONS: We found the increasing MPI was associated with increasing 24-hour mean systolic BP in children with EH. Therefore, MPI may have utility as a single, quick, noninvasive method of detection and tracking of subclinical hypertensive heart disease.

Childhood-Onset Essential Hypertension and the Family Structure.

The prevalence and effect of single-parent families in childhood-onset essential hypertension (EH) is unknown. Children with EH and age-, sex-, and ethnicity-matched controls were enrolled. Family structure data were obtained by in-person interview. A total of 148 families (76 hypertension probands, 72 control probands; median 14 years) were prospective-ly enrolled in the study. Single-parent status was seen in 42% of the families--with and without EH (38% vs 46%, P=.41; odds ratio, 0.7; 95% confidence interval, 0.4-1.4). After multivariable analysis, a statistically significant sociofamilial contributor to the development of childhood-onset EH was not identified. A significant number of single-parent families (42%), the majority with single mothers, were found in our pedigree study. Sociofamilial factors are known to contribute to the expression of adult-onset EH, but findings in our study suggest that they appear to contribute less in the expression of childhood-onset EH.

Immunoglobulin Resistance in Kawasaki Disease.

Background: The aim of this study was to identify risk factors for immunoglobulin resistance, including clinical symptoms such as arthritis and the pH of intravenous immunoglobulin. Methods: The data of children with Kawasaki disease who had received immunoglobulin were evaluated. Data regarding the brand of immunoglobulin administered were abstracted from the pharmacy records. Results: Eighty consecutive children with Kawasaki disease were evaluated (Mdnage=28 months, 66% male). The prevalence of immunoglobulin resistance was 30%. Arthritis was a presenting symptom in the acute phase of Kawasaki disease in 8% (6/80, all male) and was seen in significant association with immunoglobulin resistance in comparison to those without arthritis (16.7% vs. 0.2%, p=0.008). Next, the immunoglobulin brand types were divided into two groups: the relatively high pH group (n=16), including Carimune (pH 6.6±0.2), and the low pH group (n=63), including Gamunex (pH 4-4.5) or Privigen (pH 4.6-5). Overall, no significant difference in immunoglobulin responsiveness was found between the low pH and the high pH groups (73% vs. 56%, p=0.193), although the low pH group showed a trend toward a larger decrease in erythrocyte sedimentation rate (p=0.048), lower steroid use (p=0.054), and lower coronary involvement (p=0.08) than those in the high pH group. Conclusions: Children presenting with arthritis in the acute phase of Kawasaki disease may be at risk for immunoglobulin resistance.

Characteristics of systemic hypertension in preterm children.

The prevalence of essential hypertension (EH) among preterm children is unknown. The authors evaluated consecutive children with a diagnosis of hypertension and prematurity (gestational age <37 weeks) in a tertiary pediatric hypertension clinic and identified 36 preterm hypertensive children. Among these preterm children, 23 were diagnosed in the neonatal intensive care unit (NICU; infantile) and 13 were diagnosed at an older age (childhood). When compared with patients with a childhood diagnosis, patients with an infantile diagnosis had a significantly lower gestational age, longer duration of hospitalization in the NICU, and a higher incidence of perinatal risk factors for hypertension. None with infantile diagnosis had EH, whereas 46% with childhood diagnosis had EH. Among premature children, systemic hypertension was either diagnosed in infancy or in childhood, with each age at diagnosis having unique risk factors and clinical course. Although 83% of preterm children had secondary hypertension, EH was diagnosed in 17% and was only seen in those diagnosed beyond infancy.

Essential hypertension vs. secondary hypertension among children.

BACKGROUND: The aim was to determine the proportions and correlates of essential hypertension among children in a tertiary pediatric hypertension clinic. METHODS: We evaluated 423 consecutive children and collected demographic and clinical history by retrospective chart review. RESULTS: We identified 275 (65%) hypertensive children (blood pressure >95th percentile per the "Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents") from 423 children referred to the clinic for history of elevated blood pressure. The remainder of the patients had normotension (11%), white coat hypertension (11%), prehypertension (10%), and pending diagnosis (3%). Among the 275 hypertensive children, 43% (n = 119; boys = 56%; median age = 12 years; range = 3-17 years) had essential hypertension and 57% (n = 156; boys = 66%; median age = 9 years; range = 0.08-19 years) had secondary hypertension. When compared with those with secondary hypertension, those with essential hypertension had a significantly older age at diagnosis (P = 0.0002), stronger family history of hypertension (94% vs. 68%; P < 0.0001), and lower prevalence of preterm birth (20% vs. 46%; P < 0.001). There was a bimodal distribution of age of diagnosis in those with secondary hypertension. CONCLUSIONS: The phenotype of essential hypertension can present as early as 3 years of age and is the predominant form of hypertension in children after age of 6 years. Among children with hypertension, those with essential hypertension present at an older age, have a stronger family history of hypertension, and have lower prevalence of preterm birth.

Detection of early diastolic alterations by tissue Doppler imaging in untreated childhood-onset essential hypertension.

The aim of the study was to determine the presence of preclinical diastolic dysfunction in hypertensive children relative to normotensive children by Tissue Doppler Imaging (TDI). We prospectively enrolled children with untreated essential hypertension in absence of any other disease and a matched healthy control group with normal blood pressure (BP); both groups confirmed by clinic BP and a 24-hour ambulatory BP monitoring. Echocardiographic diastolic parameters were determined using spectral transmitral inflow Doppler, flow propagation velocity, TDI, and systolic parameters were determined via midwall shortening fraction and ejection fraction. A total of 80 multiethnic children were prospectively enrolled for the study: 46 hypertensive (median age, 13 years; 72% males) and 34 control (median age, 14 years; 65% males). The only echocardiography parameters that had a statistically significant change compared with the control children, were regional mitral Ea, Aa, and the E/Ea ratio by TDI. In comparison with controls, hypertensive children had lower Ea and Aa velocities of anterior and posterior walls and higher lateral wall E/Ea ratio. The decrease in posterior wall Ea and Aa remained significant after adjustment for gender, age, body mass index, ethnicity, and left ventricular hypertrophy on multivariate analysis. The lateral and septal wall E/Ea ratios correlated significantly with fasting serum insulin levels on similar multivariate analysis. Decreased regional TDI velocities were seen with preserved left ventricular systolic function even when other measures of diastolic dysfunction remained unchanged in untreated hypertensive children. Hypertension and serum insulin levels had strong associations with preclinical diastolic alterations in children.

Aortic dilatation in children with systemic hypertension.

The aim of the study was to determine the presence of aortic dilatation in hypertensive children, the prevalence of which is 4% to 10% in hypertensive adults. Prospectively enrolled multiethnic children, untreated for their hypertension, underwent an echocardiogram to exclude congenital heart disease and evaluate for end-organ damage and aortic size. The aorta was measured in the parasternal long-axis view at three levels: the sinus of Valsalva, supra-tubular junction, and the ascending aorta. Aortic dilatation was determined by z-score >2 at any one of the levels measured. Hypertension was defined as blood pressure above the 95th percentile based on the Fourth Working Group criteria confirmed by 24-hour ambulatory blood pressure monitoring. Among 142 consecutive hypertensive children (median age, 14 years; 45% females) aortic dilatation was detected in 2.8% (95% confidence interval, 1%-7%; median age, 16 years; 100% females). Children with aortic dilatation, when compared with those without, had significantly more aortic valve insufficiency (P = .005) and left ventricular hypertrophy (P = .018). Prevalence of aortic dilatation was 2.8% and was associated with significantly more aortic insufficiency and left ventricular hypertrophy in comparison to those without aortic dilatation.

Systemic hypertension requiring treatment in the neonatal intensive care unit.

OBJECTIVES: To determine the difference in the risk factors for systemic hypertension in preterm and term infants in the neonatal intensive care unit (NICU). STUDY DESIGN: Data were collected from an existing database of NICU children and confirmed by chart review. Systemic hypertension was defined when 3 separate measurements of systolic and/or diastolic blood pressure were >95th percentile and an antihypertensive medication was administered for >2 weeks in the NICU. RESULTS: Of 4203 infants, we identified 53 (1.3%) with treated hypertension, of whom 74% were preterm, 11% required surgical intervention, and 85% required medications on discharge. The presence of a patent ductus arteriosus, umbilical catheterization, left ventricular hypertrophy, hypertensive medication at discharge, and mortality was similar between the term and preterm infants. The major risk factors for preterm infants, especially those <28 weeks' gestation, were bronchopulmonary dysplasia and iatrogenic factors, but, in term infants, they were systemic diseases. Term infants were diagnosed with hypertension earlier during hospitalization, had a shorter duration of stay in the NICU, and had a higher incidence of hypertension needing >3 medications than preterm infants. CONCLUSIONS: Perinatal risk factors are significant contributors to infantile hypertension. Term infants were diagnosed with hypertension earlier, had a shorter duration of stay, and had a higher incidence of resistant hypertension than preterm infants.

Cardiac troponin I after cardiopulmonary bypass in infants in comparison with older children.

OBJECTIVE: At the present time, there is a trend towards performing open heart surgery at a younger age. Myocardium of infants has been thought to be more vulnerable to cardiopulmonary bypass in comparison with adults. For this study, we evaluated the degree of myocardial injury by measurement of cardiac troponin levels in infants in comparison with older children for similar surgeries. METHODS: Serum was collected before bypass, after bypass, and daily after surgery and serum cardiac troponin I level (micrograms per litre). The demographic data, cardiac diagnoses, types of surgery performed, and peri-operative parameters were collected. RESULTS: Of the 21 children enrolled consecutively, five were infants. Among the 21 patients, four patients had post-operative peak troponin values greater than 100 (three were infants) and all four patients survived and had normal left ventricular systolic function upon discharge echocardiogram. The five infants had peak troponin levels of 222.3, 202, 129, 26.7, and 82.3. The post-operative peak troponin levels were significantly higher in infants (mean 132.5 with a standard deviation of 81.6) than in the older children (mean 40.3 with a standard deviation of 33.4), although there was no significant difference in bypass time, bypass temperature, cross-clamp time, or the length of stay in the intensive care unit between the two age groups. CONCLUSIONS: Higher troponin release is seen in infants in comparison with older children after bypass for similar surgeries. A troponin level greater than 100 after bypass does not necessarily predict death or a severe cardiovascular event in the very young.

Sudden unexplained cardiac arrest in apparently healthy children: a single-center experience.

This study aimed to determine the causes of sudden cardiac arrest (SCA) in apparently healthy children at a single center in the era of primary prevention (screening questionnaire [SQ]) and secondary prevention (automated external defibrillator [AED] and the automated implantable cardioverter defibrillator [AICD]). Any child 0 to 18 years of age without prior known disease, except for attention deficit disorder, who underwent out-of-the hospital cardiopulmonary resuscitation was included in the study as a SCA subject. A retrospective chart review was used to evaluate the efficacy of the SQ, electrocardiogram (ECG), chest roentgenogram (CXR), and echocardiogram. The findings showed that for 44 of 6,656 children admitted to intensive care with SCA, an AED was used for 39%, an AICD was placed in 18%,and survival to hospital discharge was 50%. The etiology for SCA was identified in 57% of the cases, mostly in those older than 1 year, and the majority of these had a cardiac etiology (50%), whereas 7% had rupture of an arteriovenous malformation. Stimulant medication use was seen in 11% of the SCA subjects. In the best-case scenario of hypothesized primary prevention, a prior SQ, CXR, ECG, or echocardiogram may have detected respectively 18, 9, 23 and 16% of the at-risk cases, and 32% of the cases may have been detected with ECG and SQ together. Based on a historical control cohort, a positive ECG was significantly higher in the children with SCA (p = 0.014). An ECG together with a screening SQ may be more effective in identifying children potentially at risk for SCA than an SQ alone.

Descriptive epidemiology of non-syndromic complete atrioventricular canal defects.

BACKGROUND: Complete atrioventricular canal defects (CAVC) are a common heart defect, but few epidemiologic studies have evaluated non-syndromic CAVC. Risk factors for non-syndromic CAVC have not been well established. METHODS: To assess the relationship between risk for non-syndromic CAVC in offspring and several sociodemographic and reproductive parental factors, including maternal diabetes and obesity, we conducted Poisson regression analyses, using data ascertained through the Texas Birth Defects Registry, a large, population-based birth defects registry. Data were evaluated for 563 non-syndromic cases with CAVC. RESULTS: Significant associations were observed between non-syndromic CAVC in offspring and maternal pregestational diabetes (adjusted prevalence ratio (aPR) 6.74; 95% confidence interval (CI) 3.67, 12.37), gestational diabetes (aPR 1.69; 95% CI 1.03, 2.79) and obesity (aPR 1.69; 95% CI 1.24, 2.30). CONCLUSIONS: Our findings add non-syndromic CAVC to the growing list of birth defects that appear to be associated with maternal diabetes and obesity.

Deterioration of cutaneous microcirculatory status of Kawasaki disease.

Kawasaki disease (KD) is associated with generalized vasculitis with a predilection for coronary artery leading to ectasia and aneurysm in some cases. The aim of this study was to noninvasively assess the cutaneous microcirculation and correlate it with the coronary artery diameter in these patients. Laser Doppler flowmetry and dynamic capillaroscopy were performed at the nailbeds to assess total cutaneous blood flow and microcirculation in children with KD, both in the afebrile phase (after the resolution of fever) and convalescent phases, in comparison to controls. The 100 subjects analyzed in this study included 64 patients with KD (33 in afebrile phase and 31 in convalescent phase) and 36 normal controls. In KD, the capillary morphology was abnormal when compared to controls, with a larger diameter of the arterial and venous limbs, a higher intercapillary distance and a decrease in the loop numbers. Significantly decreased capillary blood cell velocity was noted in afebrile phase but not in convalescent phase. In the afebrile phase, a decreased capillary blood cell velocity significantly correlated with an increased coronary artery diameter. In conclusion, KD patients, both in the afebrile and convalescent phases, exhibited morphologic alterations in the microcirculation when compared to the controls. The results indicate the potential role of dynamic capillaroscopy for the noninvasive survey of microcirculation abnormalities in patients with KD.