scholarly journals Clinical Spectrum of SCN5A Channelopathy in Children with Primary Electrical Disease and Structurally Normal Hearts

Genes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 16
Author(s):  
Teresa Villarreal-Molina ◽  
Gabriela Paola García-Ordóñez ◽  
Álvaro E. Reyes-Quintero ◽  
Mayra Domínguez-Pérez ◽  
Leonor Jacobo-Albavera ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Sick Sinus Syndrome ◽  
Age Of Onset ◽  
Severe Disease ◽  
Overlap Syndrome ◽  
Cardiac Conduction ◽  
Incomplete Penetrance ◽  
Α Subunit ◽  
Male Predominance ◽  
Mutation Carriers

Sodium voltage-gated channel α subunit 5 (SCN5A)-mutations may cause an array of arrhythmogenic syndromes most frequently as an autosomal dominant trait, with incomplete penetrance, variable expressivity and male predominance. In the present study, we retrospectively describe a group of Mexican patients with SCN5A-disease causing variants in whom the onset of symptoms occurred in the pediatric age range. The study included 17 patients with clinical diagnosis of primary electrical disease, at least one SCN5A pathogenic or likely pathogenic mutation and age of onset <18 years, and all available first- and second-degree relatives. Fifteen patients (88.2%) were male, and sixteen independent variants were found (twelve missense, three truncating and one complex inframe deletion/insertion). The frequency of compound heterozygosity was remarkably high (3/17, 17.6%), with early childhood onset and severe disease. Overall, 70.6% of pediatric patients presented with overlap syndrome, 11.8% with isolated sick sinus syndrome, 11.8% with isolated Brugada syndrome (BrS) and 5.9% with isolated type 3 long QT syndrome (LQTS). A total of 24/45 SCN5A mutation carriers were affected (overall penetrance 53.3%), and penetrance was higher in males (63.3%, 19 affected/30 mutation carriers) than in females (33.3%, 5 affected/15 carriers). In conclusion, pediatric patients with SCNA-disease causing variants presented mainly as overlap syndrome, with predominant loss-of-function phenotypes of sick sinus syndrome (SSS), progressive cardiac conduction disease (PCCD) and ventricular arrhythmias.

CIScoSI Study [Children Immunization Status and cases of Systemic Illness]

2018 ◽  
Vol 3 (3) ◽  
Keyword(s):  
Infectious Diseases ◽  
East Asia ◽  
Pediatric Patients ◽  
Severe Disease ◽  
Tertiary Care ◽  
Immunization Coverage ◽  
South East Asia ◽  
Immunization Status ◽  
Tertiary Care Hospitals ◽  
Total Coverage

To determine the immunization status of pediatric patients under age of 5 years visiting pediatric department of tertiary care hospitals in South East Asia. The aim of this study was to appreciate the awareness and implementation of vaccination in pediatric patients who came into pediatric outpatient Department with presenting complain other than routine vaccination. we can also know the count of patients who do not complete their vaccination after birth. we can differentiate between vaccinated and unvaccinated patients and incidence of severe disease in both groups. Immunization is a protective process which makes a person resistant to the harmful diseases prevailing in the community, typically by vaccine administration either orally or intravenously. It is proven for controlling and eliminating many threatening diseases from the community. WHO report that licensed vaccines are available for the prevention of many infectious diseases. After the implementation of effective immunization the rate of many infectious diseases have declined in many countries of the world. South-East Asia is far behind in the immunization coverage. An estimated total coverage is 56%-88% for a fully immunized child, which is variable between countries. Also the coverage is highest for BCG and lowest for Polio.

scholarly journals POS1018 IMPORTANCE OF LATERAL SPINE VIEW IN DXA BONE DENSITOMETRY IN PATIENTS WITH SPONDYLOARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 776.3-777
Author(s):  
S. Miri ◽  
H. Ferjani ◽  
K. Maatallah ◽  
A. Kasraoui ◽  
D. Kaffel ◽  
...  
Keyword(s):  
Femoral Neck ◽  
Structural Changes ◽  
Age Of Onset ◽  
Posterior Part ◽  
Lateral View ◽  
Mineral Density ◽  
Lateral Spine ◽  
Male Predominance ◽  
T Score ◽  
The Mean

Background:Osteoporosis is an increasingly important health problem among patients with spondyloarthritis (SPA). The Measure of Bone Mineral Density BMD is routinely carried out in an anteroposterior (AP) view of the spine. However, the syndesmophytes, ligaments calcifications, and the posterior part of vertebrae affect AP scanning. A lateral spine view is a more sensitive tool in assessing bone loss in trabecular bone.Objectives:We aimed to evaluate the association between lateral lumbar DXA and syndesmophyte grading in patients with SPA.Methods:We conducted a retrospective study including 75 patients with SPA. Bone density of the hip and lumbar spine was measured with a GE Lunar Prodigy Advance Bone Densitometer equipment. All patients had lumbar lateral, AP, and proximal femur DXA scans. The T-score, which measures the difference between a patient’s BMD and young-normal subjects, was computed and age-matched.Results:The mean age of the patients was 36±11 years. Male predominance was noted with a sex ratio of 4.76. The mean BMI was 25±5 kg/m2. Eight percent were obese. Fifty-two percent had Vitamin D deficiency.Forty-eight percent of the patients had axial SPA, while 52% had axial and peripheral symptoms.The mean age of onset was 27±7 years. Fifty-two percent of the patients had high inflammatory biomarkers. The BASDAI, ASDAS-VS, and ASDAS-CRP mean levels were respectively: 3.5±2.4, 3.1±0.9, and 3±0.8. The mean BASRI and mass were respectively 8 + 4.8 and 16.4 + 19.4. Analyses of T-score values obtained over the femoral neck revealed osteoporosis in 18.7% of the cases and osteopenia in 32% of the cases. On the other hand, analyses of AP, spine views revealed osteoporosis in 25.3% and osteopenia in 45.3% of patients (p=0.028, r=0.254). We detected the highest percentage of osteoporosis in lateral lumbar view and T-scores matched more closely with femoral neck values; osteoporosis in 29.3%, and osteopenia in 22.7% of the patients (p<10-3, r=0.562). BMD measured in AP, and lateral views were in good agreement (p<10-3, p=0.592). Age was inversely but not significantly associated with BMD in lateral (p=0.442, r=-0.09), AP (p=0.319, r=-0.117) and femoral neck projections (p=0.179, r=-0.157). Femoral neck BMD was associated with the activity of SPA (ASDAS vs (p=0.027, r= -0.295), and the mobility limitation BASMI (p=0.032, r= -0.247). Coxitis, BASRI, or mSASS were independent of BMD.Conclusion:We conclude that spine lateral view in DXA accurately measures BMD exceeding the AP spine views and femoral neck values. Therefore, structural changes do not affect this measurementDisclosure of Interests:None declared.

Common genetic variants contribute to incomplete penetrance: evidence from cancer-free BRCA1 mutation carriers

2019 ◽  
Vol 107 ◽  
pp. 68-78 ◽  
Author(s):  
Bradley Downs ◽  
Simon Sherman ◽  
Jian Cui ◽  
Yeong C. Kim ◽  
Carrie Snyder ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Brca1 Mutation ◽  
Incomplete Penetrance ◽  
Mutation Carriers ◽  
Common Genetic Variants

scholarly journals Patients with neuromyelitis optica have a more severe disease than patients with relapsingremitting multiple sclerosis, including higher risk of dying of a demyelinating disease

2013 ◽  
Vol 71 (5) ◽  
pp. 275-279 ◽  
Author(s):  
Denis Bernardi Bichuetti ◽  
Enedina Maria Lobato de Oliveira ◽  
Nilton Amorin de Souza ◽  
Mar Tintoré ◽  
Alberto Alain Gabbai
Keyword(s):  
Multiple Sclerosis ◽  
Neuromyelitis Optica ◽  
Disease Duration ◽  
Demyelinating Disease ◽  
Age Of Onset ◽  
Severe Disease ◽  
Expanded Disability Status Scale ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

Although neuromyelitis optica (NMO) is known to be a more severe disease than relapsing-remitting multiple sclerosis (RRMS), few studies comparing both conditions in a single center have been done.Methods:Comparison of our previously published cohort of 41 NMO patients with 177 RRMS patients followed in the same center, from 1994 to 2007.Results:Mean age of onset was 32.6 for NMO and 30.2 for RRMS (p=0.2062) with mean disease duration of 7.4 years for NMO and 10.3 years for RRMS. Patients with NMO had a higher annualized relapse rate (1.0 versus 0.8, p=0.0013) and progression index (0.9 versus 0.6, p≪0.0001), with more patients reaching expanded disability status scale (EDSS) 6.0 (39 versus 17%, p=0.0036). The odds ratio for reaching EDSS 6.0 and being deceased due to NMO in comparison to RRMS were, respectively, 3.14 and 12.15.Conclusion:Patients with NMO have a more severe disease than patients with RRMS, including higher risk of dying of a demyelinating disease.

scholarly journals Graves Disease in Childhood

2021 ◽  
Author(s):  
Madhukar Mittal ◽  
Vanishri Ganakumar
Keyword(s):  
Thyroid Hormone ◽  
Side Effects ◽  
Age Of Onset ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Thyroid Stimulating Hormone ◽  
Graves Disease ◽  
Older Children ◽  
Prepubertal Children ◽  
Pediatric Age Group

Graves’ disease (GD) is an autoimmune disease caused by autoantibodies against thyroid stimulating hormone receptor (TSH-R), resulting in stimulation of thyroid gland and overproduction of thyroid hormones resulting in clinical manifestations. It is uncommon in children and is 6 times more prevalent in females. The symptomatology, clinical and biochemical severity are a function of age of onset of disease. Prepubertal children tend to present with weight loss and bowel frequency, associated with accelerated growth and bone maturation. Older children are more likely to present with the classical symptoms of thyrotoxicosis like palpitations, tremors and heat intolerance. Prepubertal children tend to have a more severe disease, longer duration of complaints and higher thyroid hormone levels at presentation than the pubertal and postpubertal children. The non-specificity of some of the symptoms in pediatric age group can lead to children being initially seen by other specialities before being referred to endocrinology. Management issues are decided based on patient’s priorities and shared decision making between patient and treating physician. Radioactive Iodine Ablation is preferred when there is relatively higher value placed on Definitive control of hyperthyroidism, Avoidance of surgery, and potential side effects of ATDs. Similarly Antithyroid drugs are chosen when a relatively higher value is placed on possibility of remission and avoidance of lifelong thyroid hormone treatment, Avoidance of surgery, Avoidance of exposure to radioactivity. Surgery is preferred when access to a high-volume thyroid surgeon is available and a relatively higher value is on prompt and definitive control of hyperthyroidism, avoidance of exposure to radioactivity and avoidance of potential side effects of ATDs. Continental differences with regards to management do exist; radio-iodine ablation being preferred in North America while Anti-thyroid drug treatment remains the initial standard care in Europe.

scholarly journals Demographic Profile and Extra Intestinal Manifestations of Ulcerative Colitis in Nepalese population: Study from TUTH a Tertiary Care Centre, Kathmandu, Nepal

2015 ◽  
Vol 4 (1) ◽  
pp. 1-5
Author(s):  
Shaneel Harsh ◽  
Ananya Adhikari ◽  
Parmatma Parazuli ◽  
Rahul Pathak ◽  
Prem K Khadga ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Age Of Onset ◽  
Severe Disease ◽  
Tertiary Care ◽  
Data Bank ◽  
Health Care Facilities ◽  
University Teaching ◽  
Cultural Variation ◽  
Tertiary Care Centre ◽  
Demographic Profile

Background and Aims: This study aims at determining the demographic profile and extra-intestinal manifestations of Ulcerative Colitis in the Nepalese patients treated in a tertiary referral centre.Methods: The study was conducted between February 1, 2014 and January 31, 2015 at the Department of Gastroenterology Tribhuvan University Teaching Hospital, Kathmandu, Nepal. The clinical and epidemiologic data from patients diagnosed to have Ulcerative Colitis were obtained and analysed.Results: During the study period, 60 patients were identified as having ulcerative colitis. Mean age at diagnosis was 34.6 years. The mean duration of illness at diagnosis was 3.7 years. Extra-intestinal manifestations (EIM) were seen in 16.6% of the patients. Sacroilitis was the most common EIM seen in11.6% followed by peripheral arthritis in 6.6% of the patients. Episcleritis, Primary Sclerosing Cholangitis and Erythema Nodosum were seen only in 1.6% each. At the time of presentation, 38.3% (n=23) had proctosigmoiditis , 50% (n=30) left sided colitis and pancolitis was seen in 11.7% (n=7).53.3% patients had mild disease, 38.3% and 8.3 % presented with moderate to severe disease respectively.Conclusion: Peak age of onset for UC in the study was third and fourth decade which was similar to the various studies from Asia and West. Musculoskeletal manifestation was the most common extra- intestinal manifestation of UC in Nepalese population. As Nepal is perhaps the most diverse country in terms of ethnicity, cultural variation, socio-economic status and health care facilities, a comprehensive nationwide data bank involving ethnicity and geographical variation is needed for a better definition of the disease characteristics.Journal of Advances in Internal Medicine 2015;04(01):1-5.

Cardiomyopathy in Cirrhotic Patients and Its Relationship with the Severity of Cirrhosis

2021 ◽  
Vol 15 (10) ◽  
pp. 2779-2782
Author(s):  
Saira Khalid ◽  
Nasir Shah ◽  
Yasir Abbas Zaidi ◽  
Muhammad Saleem Hasan ◽  
Saqib Jahangir ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Severe Disease ◽  
P Value ◽  
Cirrhotic Cardiomyopathy ◽  
Male Predominance ◽  
Class A ◽  
Class B ◽  
Cirrhotic Patients ◽  
The Mean ◽  
Class C

Study Objectives: To determine the frequency of cirrhotic cardiomyopathy in patients with liver cirrhosis and to compare it across varying grades of cirrhosis on Child Turcotte Pugh classification. Study Design and Settings: It was a descriptive cross-sectional study carried at Department of Medicine, Lahore General Hospital Lahore over 1 year from Jan 2018 to Dec 2018. Patients and Methods: The present research involved 100 male and female patients aged between 16-70 years having liver cirrhosis diagnosed at least 6 months ago. These patients underwent echocardiographic screening of cardiomyopathy which was diagnosed by the presence of diastolic dysfunction (i.e. increased E/A ratio>1). An informed written consent was obtained from every patient. Results of the Study: There was a male predominance (M:F, 1.6:1) among cirrhotic patients with a mean age of 51.9±9.8 years. The mean BMI was 26.5±3.7 Kg/m2 while the mean duration of cirrhosis was 22.0±10.9 months. Majority (49.0%) of the patients belonged to CTP Class C followed by Class-B (39.0%) and Class-A (12.0%). Cirrhotic cardiomyopathy was observed in 41.0% patients with cirrhosis. There was statistically insignificant difference in the observed frequency of cirrhotic cardiomyopathy among various subgroups of cirrhotic patients depending upon patient’s age (p-value=0.928), gender (p-value=0.997), BMI (p-value=0.983) and duration of disease (p-value=0.782). However, it increased considerably with worsening of disease on CTP Classification; Class-A vs. Class-B vs. Class-C (8.3% vs. 35.9% vs. 53.1%; p-value=0.013). Conclusion: Cirrhotic cardiomyopathy was observed in a substantial proportion of cirrhotic patients and was more frequent in patients with more severe disease which warrants routine echocardiographic screening of cirrhotic patients so that timely recognition and anticipated treatment of this complication may improve the case outcome in future medical practice. Keywords: Cirrhosis, Cardiomyopathy, Child Turcotte Pugh Class

scholarly journals Cardiac sodium channel, its mutations and their spectrum of arrhythmia phenotypes

2016 ◽  
Vol 26 (3) ◽  
pp. 281 ◽  
Author(s):  
Andrés Ricardo Pérez-Riera ◽  
Rodrigo Daminello Raimundo ◽  
Rodrigo Akira Watanabe ◽  
José Luiz Figueiredo ◽  
Luiz Carlos de Abreu
Keyword(s):  
Sodium Channel ◽  
Cardiac Muscle ◽  
Heart Function ◽  
Heart Diseases ◽  
Cardiac Conduction ◽  
Activation Process ◽  
Α Subunit ◽  
Cardiac Sodium Channel ◽  
Wide Range ◽  
Scn5a Gene

The mechanisms of cellular excitability and propagation of electrical signals in the cardiac muscle are very important functionally and pathologically. The heart is constituted by three types of muscle: atrial, ventricular, and specialized excitatory and conducting fi bers. From a physiological and pathophysiological point of view, the conformational states of the sodium channel during heart function constitute a signifi cant aspect for the diagnosis and treatment of heart diseases. Functional states of the sodium channel (closed, open, and inactivated) and their structure help to understand the cardiac regulation processes. There are areas in the cardiac muscle with anatomical and functional differentiation that present automatism, thus subjecting the rest of the fi bers to their own rhythm. The rate of these (pacemaker) areas could be altered by modifi cations in ions, temperature and especially, the autonomic system. Excitability is a property of the myocardium to react when stimulated. Another electrical property is conductivity, which is characterized by a conduction and activation process, where the action potential, by the all-or-nothing law, travels throughout the heart. Heart relaxation also stands out as an active process, dependent on the energetic output and on specificion and enzymatic actions, with the role of sodium channel being outstanding in the functional process. In the gene mutation aspects that encode the rapid sodium channel (SCN5A gene), this channel is responsible for several phenotypes, such as Brugada syndrome, idiopathic ventricular fibrillation, dilated cardiomyopathy, early repolarization syndrome, familial atrial fibrillation, variant 3 of long QT syndrome, multifocal ectopic ventricular contractions originating in Purkinje arborizations, progressive cardiac conduction defect (Lenègre disease), sudden infant death syndrome, sick sinus syndrome, sudden unexplained nocturnal death syndrome, among other sodium channel alterations with clinical overlapping. Finally, it seems appropriate to consider the “sodium channel syndrome” (mutations in the gene of the α subunit of the sodium channel, SCN5A gene) as a single clinical entity that may manifest in a wide range of phenotypes, to thus have a better insight on these cardiac syndromes and potential outcomes for their clinical treatment.

Tumor Necrosis Factor–α Promoter −308/238 Polymorphism Association with Less Severe Disease in Ankylosing Spondylitis is Unrelated to Serum TNF-α and Does Not Predict TNF Inhibitor Response

2014 ◽  
Vol 41 (8) ◽  
pp. 1675-1682 ◽  
Author(s):  
Johannes C. Nossent ◽  
Sylvia Sagen-Johnsen ◽  
Gunnstein Bakland
Keyword(s):  
Ankylosing Spondylitis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Age Of Onset ◽  
Severe Disease ◽  
Sandwich Elisa ◽  
Tnf Inhibitor ◽  
Cross Sectional ◽  
Tnf Α ◽  
Necrosis Factor

Objective.Despite the clinical efficacy of tumor necrosis factor inhibitors (TNFi), the manner in which TNF-α contributes to disease in patients with ankylosing spondylitis (AS) remains unresolved. We investigated the relationship between TNF-α gene promoter region polymorphism, serum TNF-α levels, and clinical phenotype.Methods.We did a cross-sectional and longitudinal cohort study in TNFi-naive patients with AS (n = 335). Clinical data and biological samples were collected during a research visit with genotyping for TNF-α −238 A/G and −308 A/G performed by Taqman RT-PCR and TNF levels determined by sandwich ELISA. Longitudinal TNF levels were monitored in unselected patients (n = 61).Results.TNF-α −308 GA/AA genotype was present in 14% and TNF-α −238 GA/AA genotype in 1% of patients. TNF-α −308 GA/AA genotype was associated with a reduced risk of uveitis and better spinal function, while TNF-α −238 GA/AA genotype was associated with later age of onset and lower erythrocyte sedimentation rate (ESR). Serum TNF-α level was lower in patients with AS (151 pg/ml) than in controls (263 pg/ml), because more patients with AS had undetectable serum TNF-α (66 vs 25%, p < 0.001). TNFi treatment did not influence serum TNF-α. There was no effect of TNF-α −308/−238 or HLA-B27 genotype on serum TNF-α or subsequent initiation of TNFi.Conclusion.TNF-α −238 or −308 GA/AA genotypes in patients with AS are associated with signs of less severe disease. Serum TNF-α is, however, undetectable in two-thirds of patients with AS and is not influenced by TNF-α promoter genotype or TNFi therapy. These data suggest a more significant role for TNF-α at local sites of inflammation in AS than through systemic effects.

Myotonic Dystrophy

2018 ◽  
Author(s):  
Andrea Johnson
Keyword(s):  
Skeletal Muscle ◽  
Cognitive Impairment ◽  
Sleep Apnea ◽  
Myotonic Dystrophy ◽  
Pediatric Patients ◽  
Autosomal Dominant ◽  
Anesthetic Management ◽  
Cardiac Conduction ◽  
Autosomal Dominant Disorder ◽  
Skeletal Muscle Weakness

Myotonic dystrophy (DM) is a multisystemic autosomal dominant disorder. Individuals may present with symptoms at any age, but pediatric patients typically will present before 10 years of age. The clinical features of DM differ depending on the type of dystrophy and include skeletal muscle weakness, myotonia, sleep apnea, decreased gastrointestinal motility, insulin hypersecretion, cardiac conduction abnormalities, and occasionally cognitive impairment. Anesthetic management of the patient with DM should begin in the preoperative arena and should take into account the postoperative considerations and concerns for the patient with DM. This chapter will help the clinician develop an appropriate anesthetic plan and implement a safe and effective perioperative experience.

Sign in / Sign up

Export Citation Format

Share Document