Investigating the Genetic Etiology of Pediatric Patients with Peripheral Hypotonia Using the Next-Generation Sequencing Method.

Background Hypotonia occurs as a result of neurological dysfunction in the brain, brainstem, spinal cord, motor neurons, anterior horn cells, peripheral nerves, and muscles. Although the genotype-phenotype correlation can be established in 15 to 30% of patients, it is difficult to obtain a correlation in most cases. Aims This study was aimed to investigate the genetic etiology in cases of peripheral hypotonia that could not be diagnosed using conventional methods. Methods A total of 18 pediatric patients with peripheral hypotonia were included. They were referred to our genetic disorders diagnosis center from the Pediatric Neurology Department with a prediagnosis of hypotonia. A custom designed multigene panel, including ACTA1 , CCDC78 , DYNC1H1 , GARS , RYR1 , COL6A1 , COL6A2 , COL6A3 , FKRP , FKTN , IGHMBP2 , LMNA , LAMA2 , LARGE1 , MTM1 , NEM , POMGnT1 , POMT1 , POMT2 , and SEPN1 , was used for genetic analysis using next-generation sequencing (NGS). Results In our study, we found 13 variants including pathogenic (two variants in LAMA2) and likely pathogenic variants (three variants in RYR1 and POMGnT1) and variants of uncertain clinical significance (eight variants in RYR1, COL6A3, COL6A2, POMGnT1 and POMT1) in 11 (61%) out of 18 patients. In one of our patients, a homozygous, likely pathogenic c.1649G > A, p.(Ser550Asn) variant was defined in the POMGnT1 gene which was associated with a muscle-eye-brain disease phenotype. Conclusion The contribution of an in-house designed gene panel in the etiology of peripheral hypotonia with a clinical diagnosis was 5.5%. An important contribution with the clinical diagnosis can be made using the targeted multigene panels in larger samples.

Seroprevalence of autoimmune thyroiditis and celiac disease in children with insulin-dependent diabetes mellitus in the Thrace region of Turkey.

BACKGROUND/AIMS: We aimed to estimate the seroprevalence of celiac disease, a gluten-sensitive enteropathy, and autoimmune thyroiditis in children with insulin-dependent diabetes mellitus in the Thrace region of Turkey. METHODS: The population studied consisted of 33 children with insulin-dependent diabetes mellitus and 41 healthy children with demographic features similar to the study subjects. Free triiodothyronine, free thyroxine, thyroid-stimulating hormone, anti-thyroid peroxidase antibody, anti-thyroglobulin antibody, IgA, anti-endomysium IgA, and anti-gliadin IgA were measured in all cases and controls. RESULTS: The serum levels of free triiodothyronine and free thyroxine were within the normal range in all cases. However, in one patient who had anti-thyroid peroxidase and antithyroglobulin antibodies, the thyroid-stimulating hormone level was high despite a normal free triiodothyronine and free thyroxine value. Ultrasonographic findings confirmed thyroiditis in this patient. Anti-thyroid peroxidase antibodies, anti-thyroglobulin antibodies, anti-endomysium IgA and anti-gliadin IgA were detected in 15.4%, 6%, 9.1% and 3% of the diabetic cases, respectively. None of these antibodies was detected in the control group. In the diabetic group, the seroprevalences of the antithyroid peroxidase antibodies and the anti-endomysium IgA were statistically higher than in the control group (p<0.05). CONCLUSIONS: Children with insulin-dependent diabetes mellitus in our region should undergo periodic screenings for autoimmune thyroiditis and celiac disease.

A cost analysis of radiologic imaging in pediatric trauma patients.

BACKGROUND: The aim of this study was to examine the cost of radiologic imaging in pediatric trauma patients admitted to the pediatric emergency department. METHODS: All patients were retrospectively evaluated according to age, gender, details of injury, radiological investigations ordered and their results, cost of radiologic imaging, length of stay, outcome of the injury, and hospitalization rates. RESULTS: The cost of radiologic imaging was retrospectively analyzed in 1231 trauma patients aged between one month and 15 years (mean 5.91 +/- 3.82 years). For the 996 patients who had radiological imaging, 3382 images were taken in total. Of these, only 300 (8.8%) were abnormal. The mean (and SD) total cost of radiologic imaging was US$ 40.42 ($34.38) (range $4.67 to $139.26). Total cost correlated inversely with Glasgow Coma Scale (GCS) (r = -0.37, p < 0.001), directly with Injury Severity Score (ISS) (r = -0.27, p < 0.001) and was not correlated with the Pediatric Trauma Score (PTS) (r = -0.16, p > 0.05). The mean (and SD) duration of hospital stays was 8.54 (10.91) hours. CONCLUSION: Advanced radiological images may help in early diagnosis of trauma cases. However, periodic education programs to prevent unnecessary radiological imaging in emergency departments are also necessary to decrease the cost of these imaging modalities.

Validity of serum tau protein levels in pediatric patients with minor head trauma.

BACKGROUND: The aim of this study was to investigate the relationship between intracranial injury and serum tau protein levels in pediatric patients with minor head trauma (MHT). METHODS: We included 60 pediatric patients with MHT (Glasgow Coma Scale [GCS], 14-15) and 28 control patients. The patients were divided into 3 groups as follows: those without (group 1) and with (group 2) intracranial lesions shown on cranial computed tomography (CCT) and the control group (group 3). RESULTS: The mean serum tau protein level was 96.06 +/- 70.36 pg/mL in group 1, whereas it was 112.04 +/- 52.66 pg/mL in group 2, with no statistically significant difference between the groups (p = .160). The mean serum tau protein levels between the study groups (group 1 and group 2) and control (38.52 +/- 29.01) were statistically significant (P < .001 and P < .001, respectively). The GCS score and pathologic condition in CCT were only influential variables on tau protein levels. CONCLUSIONS: We found that serum tau protein increased after MHT but did not distinguish between those with and those without intracranial lesions demonstrable on CCT.

Indications for brain computed tomography and hospital admission in pediatric patients with minor head injury: how much can we rely upon clinical findings?

OBJECTIVES: The aim of this study was to describe the characteristics of patients with a minor head injury (MHI) who were admitted to a pediatric emergency unit and to identify the clinical signs and symptoms that most reliably predict the need for cranial computed tomography (CCT) and hospital admission following MHI. METHODS: All patients were retrospectively evaluated according to age, gender, details of injury, presenting symptoms, physical examination findings, radiological investigations ordered and results, length of stay, outcome of the injury and hospitalization rates. RESULTS: The factors affecting indications for computed tomography and hospitalization were retrospectively analyzed in 916 patients--585 males and 331 females, aged between 1 month and 15 years (mean: 5.01 +/- 3.58 years), with MHI. A multivariate analysis revealed significant correlations between CCT abnormalities and Glasgow Coma Scale scores of 13 or 14, headache, posttraumatic amnesia, blurred vision, cephalohematomas, periorbital ecchymoses, otorrhea and abnormal neurological findings. CCT abnormalities were identified in 67 (19.8%) of the 338 CCT scans. Twenty of the 67 patients (29.9%) with CCT scan abnormality had no clinical signs. Of all cases, 125 (13.6%) were hospitalized, 617 (67.4%) were treated as outpatients, and 174 (19.0%) left the emergency department based on a personal decision. CONCLUSION: Some clinical risk factors can be used as predictors of abnormalities in CCT scans following MHI, but the absence of such clinical findings does not exclude the possibility of intracranial injuries.

Scalds in pediatric emergency department: a 5-year experience.

Scald injuries are the most common type of burn in childhood. The authors' aim in this study was to determine the characteristics of scald burns and to identify clinical signs and symptoms which help to predict the indications for hospitalization after scalding burn injury. All patients were retrospectively evaluated according to gender, ages, cause of burn, burn size and depth, distribution of burn area, first aid given, management, and patient's outcomes. The factors affecting indication for hospitalization were retrospectively analyzed in 165 patients, 95 males and 70 females aged 1 month to 13 years (mean 2.74 +/- 2.44 years), with scalding burn injury. The most common cause of scald injuries were hot water (106 patients) or hot tea and coffee (39 patients). The mean percent of TBSA burned was 10.26 +/- 7.26%. Sixty-nine patients had required hospitalization. In the multivariate logistic regression analyses, among study subjects, only age and TBSA were risk factors significantly correlated to hospitalization (P < .001, P < .01, respectively). Prevention of scald injuries will require a two-prolonged approach: educating families and changing the traditional methods of preparing soup, milk, and tea in Turkey and elsewhere. To create effective programs for preventing scald injuries, it is essential to consider ethnic, cultural, socioeconomic, and environmental factors based on these characteristics.

Preventive effects of curcumin on different aspiration material-induced lung injury in rats.

PURPOSE: We have studied whether curcumin protects different pulmonary aspiration material-induced lung injury in rats. MATERIALS AND METHODS: The experiments were designed in 60 Sprague-Dawley rats, randomly allotted into one of six groups (n=10): normal saline (NS, control), enteral formula (Biosorb Energy Plus, BIO), hydrochloric acid (HCl), NS+curcumin-treated, BIO+curcumin-treated, and HCl+curcumin-treated. NS, BIO, HCl were injected in to the lungs. The rats received curcumin twice daily only for 7 days. Seven days later, both lungs in all groups were examined histopathologically, immunohistochemically, and biochemically. Histopathologic examination was performed according to the presence of peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, alveolar exudate, alveolar histiocytes, interstitial fibrosis, granuloma, and necrosis formation. Immunohistochemical assessments were examined for the activity of inducible nitric oxide synthase (iNOS) and the expression of surfactant protein D (SP-D). Malondialdehyde (MDA), hydroxyproline (HP), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity were measured in the lung tissue. RESULTS: Our findings show that curcumin inhibits the inflammatory response reducing significantly (P<0.05) all histopathological parameters in different pulmonary aspiration models. Pulmonary aspiration significantly increased the tissue HP content, MDA levels and decreased the antioxidant enzyme (SOD, GSH-Px) activities. Curcumin treatment significantly decreased the elevated tissue HP content, and MDA levels and prevented inhibition of SOD, and GSH-Px enzymes in the tissues. Furthermore, our data suggest that there is a significant reduction in the activity of iNOS and a rise in the expression of SP-D in lung tissue of different pulmonary aspiration models with curcumin therapy. CONCLUSION: Our findings support the use of curcumin as a potential therapeutic agent in acute lung injury.

Protective effects of S-methylisothiourea sulfate on different aspiration materials-induced lung injury in rats.

OBJECTIVES: The aim of this study was to evaluate the efficiency of inducible nitric oxide synthase (iNOS) specific inhibitor, S-methylisothiourea sulfate (SMT) in preventing lung injury after different pulmonary aspiration materials in rats. MATERIAL AND METHODS: The experiments were performed in 80 Sprague-Dawley rats, ranging in weight from 220 to 250 g, randomly allotted into one of the eight groups (n=10): normal saline (NS, control), Biosorb Energy Plus (BIO), sucralfate (SUC), hydrochloric acid (HCl), NS+SMT treated, BIO+SMT treated, SUC+SMT treated, and HCl+SMT treated. NS, BIO, SUC, HCl were injected in to the lungs in a volume of 2 ml/kg. The rats received twice daily intraperitoneal injections of 20 mg(kg day) SMT (Sigma Chemical Co.) for 7 days. Seven days later, rats were killed, and both lungs in all groups were examined immunohistochemically and histopathologically. RESULTS: Our data show that SMT inhibits the inflammatory response significantly reducing (p<0.05) peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, alveolar exudate, alveolar histiocytes, interstitial fibrosis, granuloma, and necrosis formation in different pulmonary aspiration models. Furthermore, our data suggest that there is a significant reduction in the activity of iNOS and arise in the expression of surfactant protein D in lung tissue of different pulmonary aspiration models with SMT therapy. CONCLUSION: It was concluded that SMT treatment might be beneficial in lung injury, therefore shows potential for clinical use.

[Evaluation of the fall-related trauma cases applied to our pediatric emergency department]. / Cocuk acil ünitemize düsme nedeniyle basvuran travma olgularinin degerlendirilmesi.

BACKGROUND: The aim of this study was to evaluate the fall-related trauma cases who were admitted to our pediatric emergency unit. METHODS: We retrospectively evaluated the files of 161 cases (100 males [62.1%], 61 females [37.9%]) who had sustained falls and were admitted to our pediatric emergency unit. Data on the patients' age, sex, arrival type, type of fall, height fallen, type of injuries, radiological findings and hospitalization rates were investigated. RESULTS: Of 161 cases mean age was 4.29+/-3.33 years and height fallen was 135+/-95 centimeters. The common types of fall were from furniture (35.4%), stairs (17.4%) and balconies and windows (11.2%). Major injuries included head trauma (84.4%), soft tissue (72.7%) and extremity (37.9%). Thirty cases (18.6%) were hospitalized, while 112 cases (69.6%) were treated as outpatient and 11.8% of them were discharged due to their own demand. CONCLUSION: The majority of fall-related injuries in childhood mostly occurs in private houses and head trauma is the most frequent injury. To decrease the frequency of the fall injuries, strategies should include parents' education about the mechanism of falls and increase prevention strategies.

[The evaluation of bicycle accidents that were admitted to a pediatric emergency department]. / Bisiklet kazasi nedeniyle çocuk acil ünitemize basvuran olgularin degerlendirilmesi.

BACKGROUND: We planned this study to evaluate trauma cases secondary to bicycle driving in childhood and to draw attention to the importance of the regulation of traffic rules, the education of bicycle drivers, and the importance of helmet usage. METHODS: Data in this study were obtained by retrospective review of the files of trauma cases admitted to the Pediatric Emergency Unit of Trakya University Medical Faculty between January 2003 and August 2005. Patients' age, gender, clinical signs, type of injury, season of the event and percentage of hospitalization were obtained from hospital records. RESULTS: Fifteen (24.6%) of 61 cases who were admitted to our emergency unit were females and 46 (75.4%) were males. The types of trauma of all patients who suffered from bicycle accidents were as following: 42 (68.9%) head trauma, 29 (47.5%) extremity trauma, 49 (80.3%) soft tissue trauma, 2 (3.3%) abdominal trauma, and one case of urogenital trauma. Also multiple traumas were present in most of these cases. Thirteen patients had extremity fractures and three had cranial fractures. None of the bicycle drivers were using helmets at the time of the trauma. CONCLUSION: Bicycle drivers should have specific education, helmet use must become widespread and special traffic regulations have to be settled.

99mTc-HMPAO brain perfusion single-photon emission computed tomography in children with Down syndrome: relationship to epilepsy, thyroid functions, and congenital heart disease.

In recent years, it has been possible for patients with Down syndrome to live longer with advanced medical treatment and social support. As a result, the problems of these patients, such as thyroid diseases, leukemia, and Alzheimer disease, would be encountered more frequently. In this study, we aimed to perform the brain perfusion of children with Down syndrome by technetium 99m hexamethylpropylene amine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) and to determine the relationship between brain perfusion and epilepsy, thyroid function tests, congenital heart disease, and level of mental and motor development. Thirty patients with Down syndrome, aged between 1 and 15 years, were included in our study. Demographic data, the existence of epilepsy and congenital heart defects, the level of mental and motor development, serum levels of thyroid hormones, and autoantibodies were determined. All patients underwent computed tomography (CT) and/or magnetic resonance imaging (MRI). Cerebral SPECT was performed in all cases to evaluate the brain perfusion pattern. According to the visual evaluation of cerebral SPECT results, hypoperfusion was detected in 11 cases (37%). Patients with cerebral hypoperfusion (group 1) and patients with normal cerebral perfusion (group 2) were compared. There was no difference between group 1 and group 2 in terms of demographic data, congenital heart defects, IQ levels, thyroid hormones, and autoantibodies, but the incidence of epilepsy was significantly higher in group 1 (P<.001). When motor and mental development levels were compared, it was found that cases in group 1 were significantly more retarded in personal-social and fine motor skills (P<.05). The present study showed that cerebral hypoperfusion in children with Down syndrome is mostly related to epilepsy and the other coexisting conditions, congenital heart disease and hypothyroidism. Patients with cerebral hypoperfusion also have more retarded developmental levels, especially in personal-social and fine motor skills.

Ceftriaxone-associated biliary pseudolithiasis in children.

PURPOSE: Ceftriaxone is known to induce reversible precipitations, known as pseudolithiasis, in the gallbladder and urinary tract. The aim of this study was to investigate the incidence and predisposing factors that contribute to this side effect. METHODS: A prospective study was conducted in 156 children admitted for the treatment of various infections with different daily ceftriaxone doses (50 mg/kg, 75 mg/kg, and 100 mg/kg). Sonographic examinations of the gallbladder and urinary tract were performed before treatment on the third and seventh day of therapy, and at the first and second month after the end of treatment. Patients with positive findings were followed with weekly sonographic examinations until the abnormality resolved. RESULTS: Abnormal gallbladder sonograms were demonstrated in 27 children (17%); 16 of them (10%) had gallbladder lithiasis, 11 had gallbladder sludge (7%) (n = 4 on the third day, n = 23 on the seventh day), and 1 developed urolithiasis (0.6%). Five children (19%) were symptomatic. The abnormalities resolved after a mean of 16 days (range 10-30 days). Patients with pseudolithiasis were older and treated with higher drug doses than those with normal sonographic findings (P < 0.01 and P < 0.05, respectively). CONCLUSIONS: Biliary pseudolithiasis (and infrequently nephrolithiasis) usually occurs in children receiving high doses of ceftriaxone. It is generally asymptomatic. When this reversible complication becomes symptomatic, unnecessary cholecystectomy should be avoided.

Factor V Leiden mutation, deficiency of antithrombin III and elevation of factor VIII in a child with ischemic stroke: a case report.

A 4-year-old boy was admitted with left hemiplegia. Thrombophilia marker examination resulted with factor V Leiden mutation heterozygosity, a deficiency of antithrombin III and a high level of factor VIII. Cranial computed tomography scan revealed an ischemic infarct in the region of right anterior cerebral artery. In the literature, combinations of multiple thrombophilia risk factors that trigger cerebral ischemic stroke in children have been emphasized. To our knowledge, this is the first child with these combinations of thrombophilia risk factors and ischemic stroke to be reported in the literature.

The prevalence of folic acid deficiency among adolescent girls living in Edirne, Turkey.

PURPOSE: A high incidence of iron-deficiency is a common observation among adolescent girls, whereas only limited data are available regarding the folic acid status of this group. This study was designed to determine the prevalence of biochemical folic acid deficiency in a group of Turkish adolescent girls. METHODS: We surveyed the serum folic acid, complete blood count, and dietary folic acid intake of Turkish adolescent girls after using three-day self-reported food intakes in urban and rural areas of Edirne, Turkey. RESULTS: A sample population was composed of 704 adolescent girls; their serum folic acid levels were found to be adequate for 37.6% (> or = 6 ng/mL), marginal for 46% (3 to 5.9 ng/mL), and at deficient levels for 16.3% (< 3 ng/mL). Folic acid deficiencies were found in 20.1% (36 of 179) and 14.7 % (61 of 416) of adolescent girls from rural and urban areas, respectively. Self-reported three-day folic acid intakes were correlated with the corresponding blood values for this nutrient. In the logistic regression analysis, three factors emerged as significant independent predictors of folic acid deficiency: low income (odds ratio [OR]: 2.4, 95% confidence interval [CI]: 1.3-4.2, p < .001), low vitamin C (OR: 1.9, 95% CI: 1.1-3.5, p < .05), and folic acid intake (OR: 4.8, 95% CI: 2.8-8.1, p < .001). CONCLUSION: Data from the present study may indicate that serum folic acid is low in a group of Turkish adolescent girls. These low values appear to be associated with low income, and low dietary intakes of folic acid and vitamin C.

Rubella seroprevalence among Turkish adolescent girls living in Edirne, Turkey.

This study was designed to estimate the rubella seroprevalence in unvaccinated Turkish adolescent girls in urban and rural areas of Edirne, and to create preventive strategies for congenital rubella syndrome (CRS). The sample, representing 12- to 17-year-old adolescent girls, consisted of 1,600 subjects selected from school lists by systematic and random sampling, which was matched by age and urban-rural residency strata proportional to the corresponding distributions in the Edirne population. For each participant, a questionnaire was completed and rubella-specific IgG antibodies were measured. After analysis of samples, seropositivity prevalence, equivocal and seronegative samples of adolescent girls in Edirne were determined as 93.1%, 0.6% and 6.3%, respectively. Data from the present study may indicate that 6.9% of adolescent girls have considerable risk for rubella infection during pregnancy. Eliminating rubella and CRS in Turkey will require national health service efforts, including vaccination of all adolescents and all susceptible women of childbearing age.

Seroprevalance of Bordetella pertussis antibodies among healthy adolescent girls in Edirne.

OBJECTIVE: Immune response against pertussis can be induced by infection and/or vaccination and vaccine induced immunity is known to wane within the decade following vaccination. Our aim was to assess the pertussis immune response among adolescent girls in the province of Edirne in Turkey. In addition we determined the relationship between the immune response and age, residence, and vaccination status. MATERIAL AND METHODS: Serum samples were collected from 359 adolescent girls, 12 to 17 years old. The subjects were selected by systematic randomisation from school rosters and sampled by age and urban-rural residence strata proportional to the corresponding distributions in the Edirne population. Pertussis immunity was determined by an in-house quantitative ELISA method for anti-PT and anti-FHA antibodies. RESULTS: Protective levels of antibody (>10 EU/ml) for anti-pertussis toxin and anti-filamentous heamagglutinin were found in 95.3% and 97.2% of the overall study group respectively. In 12- to 14-year-olds protective levels were shown in 94.1% and 97.0%, in 15- to 17-year-olds in 97.5% and 97.5%, in rural areas in 96.7% and 97.5%, and in urban areas in 94.5% and 97.5%, respectively (p >0.05). CONCLUSION: The high percentages of protective levels of antibodies in our study population might be an indicator of previous infections, which are a threat to infants who have not completed primary immunisation. In this respect, adult immunisation should be considered.

99mTc-HMPAO single photon emission computed tomography (SPECT) in both asphyxiated and epileptic children with or without status epilepticus.

In this study, technetium 99m hexamethylpropyleneamine oxime (99mTc-HMPAO) single photon emission computed tomography (SPECT) was performed on 18 asphyxiated and epileptic children who also had a status epilepticus episode, and the results were compared with those for 21 children without a status epilepticus episode. All patients underwent a detailed neurologic history, interictal electroencephalography, computed tomography, and/or magnetic resonance imaging. Visual evaluation of the SPECT study showed that 16 patients of group 1 had 56 hypoperfused regions in cerebral blood flow. However, in group 2, visual evaluation showed only six detectable hypoperfusion areas in five patients. When an asymmetric index value of 3 was considered as a cutoff point, 82 regions in group 1 and 57 regions in group 2 were above this value after the quantitative SPECT evaluation. The mean number of pathologic brain regions was found to be higher in group 1 (5.1 +/- 4.3) than in group 2 (2.7 +/- 2.4) (P = .014). The localization of hypoperfused regions that were observed in temporal and frontal regions was generally similar in both groups. In conclusion, the functional activities of the brain vary in both asphyctic and epileptic children, with and without status epilepticus. These children might be candidates for refractory convulsive disease, and interictal SPECT can be a reliable method for the detection of brain lesions in these patients.

Factor V Leiden mutation and other thrombophilia markers in childhood ischemic stroke.

The aim of this study was to evaluate the association between ischemic childhood stroke and thrombophilia. The prevalence of thrombophilia risk factors in 30 unrelated children with ischemic stroke were compared with 33 age-matched control subjects. Patients and control group were tested for the presence of activated protein C (APC) resistance, antiphospholipid antibodies (APLA), increased factor VIII levels, and for the deficiency of protein C (PC), protein S (PS), and antithrombin. When APCR was detected in patients or in controls, factor V Leiden (FVL) mutation was also tested. Seventeen of 30 patients (56.6%) had at least one thrombophilia marker compared with only 5 of 33 control subjects (15.1%). Three children with ischemic stroke (10%) were affected with a combination of two or more thrombophilia markers whereas none of the children in the control group had a combination of risk factors. Seven of 30 children with ischemic stroke (23.3%) and one of 33 control subjects (3.03%) had APC resistance and in all of them FVL mutation were found. The prevalence of FVL mutation was higher among pediatric stroke patients than among control subjects (p < 0.05). None of the patients but one child from the control group (3.03%) had PS deficiency. Antithrombin and PC deficiencies and the presence of APLA and increased factor VIII levels were more frequent in the pediatric stroke patients than in controls but the difference was not statistically significant (p > 0.05). These data confirm that stroke in children is commonly associated with a combination of multiple risk factors and especially the prevalence of FVL mutation is increased in children with ischemic stroke compared with control subjects.