Atrioventricular canal defect and associated genetic disorders: new insights into polydactyly syndromes

Atrioventricular canal defect (AVCD) is a common congenital heart defect (CHD), representing 7.4% of all cardiac malformations, considered secondary to an extracellular matrix anomaly. The AVCD is associated with extracardiac defects in about 75% of the cases. In this review we analyzed different syndromic AVCDs, in particular those associated with polydactyly disorders, which show remarkable genotype-phenotype correlations. Chromo - some imbalances more frequently associated with AVCD include Down syndrome, deletion 8p23 and deletion 3p25, while mendelian disorders include Noonan syndrome and related RASopathies, several polydactyly syndromes, CHARGE and 3C (cranio-cerebello-cardiac) syndrome. The complete form of AVCD is prevalent in patients with chromosomal imbalances. Additional cardiac defects are found in patients affected by chromosomal imbalances different from Down syndrome. Left-sided obstructive lesions are prevalently found in patients with RASopathies. Patients with deletion 8p23 often display AVCD with tetralogy of Fallot or with pulmonary valve stenosis. Tetralogy of Fallot is the only additional cardiac defect found in patients with Down syndrome and AVCD. On the other hand, the association of AVCD and tetralogy of Fallot is also quite characteristic of CHARGE and 3C syndromes. Heterotaxia defects, including common atrium and anomalous pulmonary venous return, occur in patients with AVCD associated with polydactyly syndromes (Ellis-van Creveld, short rib polydactyly, oral-facial-digital, Bardet-Biedl, and Smith-Lemli-Opitz syndromes). The initial clinical evidence of anatomic similarities between AVCD and heterotaxia in polydactyly syndromes was corroborated and explained by experimental studies in transgenic mice. These investigations have suggested the involvement of the Sonic Hedgehog pathway in syndromes with postaxial polydactyly and heterotaxia, and ciliary dysfunction was detected as pathomechanism for these disorders. Anatomic differences in AVCD in the different groups are probably due to different genetic causes

Clinical characteristics and risk of arrhythmic events in patients younger than 12 years diagnosed with Brugada syndrome

Background Brugada syndrome (BrS) is an inheritable disease with an increased risk of sudden cardiac death. Although several score systems have been proposed, the management of children with BrS has been inconsistently described. Objective The purpose of this study was to identify the characteristics, outcome, and risk factors associated with cardiovascular and arrhythmic events (AEs) in children younger than 12 years with BrS. Methods In this single-center case series, all children with spontaneous or drug/fever-induced type 1 Brugada electrocardiographic (ECG) pattern and younger than 12 years at the time of diagnosis were enrolled. Results Forty-three patients younger than 12 years at the time of diagnosis were included. The median follow-up was 3.97 years (interquartile range 2–12 years). In terms of first-degree atrioventricular block, premature beats, nonmalignant AEs, malignant AEs, and episodes of syncope, no significant differences were observed either between patients with spontaneous and drug/fever-induced type 1 Brugada ECG pattern or between female and male patients (except a significant difference between female and male patients for first-degree atrioventricular block). A higher incidence of malignant AEs was observed in patients with syncope (3 of 8 [37.5%] vs 0 of 35 [0%]; P = .005) than in patients without syncope. SCN5A mutations were associated with a higher occurrence of malignant AEs (3 of 14 [21.4%] vs 0 of 25 [0%]; P = .04) compared with no SCN5A mutations. Conclusion A spontaneous type 1 Brugada ECG pattern is not associated with a higher incidence of syncope, first-degree atrioventricular block, premature beats, nonmalignant AEs, and malignant AEs than the drug/fever-induced type 1 Brugada ECG pattern. Syncope events are correlated with an increased incidence of malignant AEs. Moreover, SCN5A mutations are associated with a higher occurrence of malignant AEs

Business Communication Strategies: Analysis of Internal Communication Processes

The purpose of this research is to investigate the current situation of internal communication in the maintenance department in the cement industry. In most organizations, employees and managers have struggled with the thought of attempting to solve weak and bad communication between the two parties which mostly cause issues to an organization, whether in performance or cost wise. This research was carried out at the maintenance department in Cement Company. A quantitative method was used to gather relevant information regarding a study of internal communication in maintenance department in cement industry. The research findings were supported that current management at Cement industry implementing team meetings effectively. The current management at Cement industry is creating and using online- printed communications tools, organizing regular events.  The research findings were supported that current management at Cement industry using online tools for internal communication. In terms of notice board communication, the researcher was not able to find any link between company’s’ standard as a fact of internal communication method and respondent’s perception as research findings. At this point the researcher was able to point out the gap between this study and the fact of internal communication at maintenance department in Cement industry.  According to the findings the researcher was able to find out the gap between site visit communication between perception and the fact. Concerns of face-to-face communication method, also, was not found in the standard of internal communication at cement industry. Accordingly, the researcher was able to point out the gap between face-to-face communication method as a fact and respondents’ perception according to the research findings. The current management at Cement industry is establishing a regular, transparent communication with all employees covering the entire organization. The research findings were supported that current management at Cement industry implementing network communication effectively

The Role of Shopping Malls on Kurdistan Regional Government’s Economy

This research covers the history of shopping malls in KRG and how the malls were a new shopping destination for the citizens of KRG. However, with the current economic crisis in KRG and the financial difficulties that people have been facing in the past two years. This research studies the impact of economy crisis on the spending\u27s of individuals and the shopping centers that were used to be filled with people who would spend a huge amount of money on shopping. We distributed 240 questionnaires in three languages: Kurdish, Arabic and English in order to identify people’s shopping behavior and the factors that attract people to the shopping malls. The things that we managed to accomplish in this research was that people are pessimistic about the financial situation and future of the economy. People would rather save their cash than spending it on shopping. These achievements met the main objective of this study which was to find out people’s behavior to do their shopping and satisfy their needs and wants that are provided in the malls

Employee Commitment: The Relationship between Employee Commitment and Job Satisfaction

The aim of the current study is to examine the association between employee commitment and job satisfaction at selected private universities in Kurdistan region of Iraq. Organizational commitment predicts work variables, for example, turnover, hierarchical citizenship conduct, and employment execution. A percentage of the elements, for example, part stretch, strengthening, work shakiness and employability, and appropriation of authority have been appeared to be associated with a laborer\u27s feeling of organizational commitment. This research was carried out at the three different private universities. A quantitative method was used to gather relevant information regarding the relationship between organizational commitment and job satisfaction. The results revealed that all three independent factors are correlated with job satisfaction. The result can be used as a guiding method for the university’s management to increase their employees’ commitment. Job satisfaction has a positive relation with employee commitment if employees are satisfied, they are organizationally committed we found that job satisfaction has a positive impact on employee commitmen

Recurrent microdeletion at 17q12 as a cause of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome: two case reports

<p>Abstract</p> <p>Background</p> <p>Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) consists of congenital aplasia of the uterus and the upper part of vagina due to anomalous development of Müllerian ducts, either isolated or associated with other congenital malformations, including renal, skeletal, hearing and heart defects. This disorder has an incidence of approximately 1 in 4500 newborn girls and the aetiology is poorly understood.</p> <p>Methods and Results</p> <p>we report on two patients affected by MRKH syndrome in which array-CGH analysis disclosed an identical deletion spanning 1.5 Mb of genomic DNA at chromosome 17q12. One patient was affected by complete absence of uterus and vagina, with bilaterally normal ovaries, while the other displayed agenesis of the upper part of vagina, right unicornuate uterus, non cavitating rudimentary left horn and bilaterally multicystic kidneys. The deletion encompassed two candidate genes, <it>TCF2 </it>and <it>LHX1</it>. Mutational screening of these genes in a selected group of 20 MRKH females without 17q12 deletion was negative.</p> <p>Conclusion</p> <p>Deletion 17q12 is a rare albeit recurrent anomaly mediated by segmental duplications, previously reported in subjects with developmental kidney abnormalities and diabetes. The present two patients expand the clinical spectrum associated with this imbalance and suggest that this region is a candidate locus for a subset of MRKH syndrome individuals, with or without renal defects.</p

Assessment of copy number variations in 120 patients with Poland syndrome

Poland Syndrome (PS) is a rare congenital disorder presenting with agenesis/hypoplasia of the pectoralis major muscle variably associated with thoracic and/or upper limb anomalies. Most cases are sporadic, but familial recurrence, with different inheritance patterns, has been observed. The genetic etiology of PS remains unknown. Karyotyping and array-comparative genomic hybridization (CGH) analyses can identify genomic imbalances that can clarify the genetic etiology of congenital and neurodevelopmental disorders. We previously reported a chromosome 11 deletion in twin girls with pectoralis muscle hypoplasia and skeletal anomalies, and a chromosome six deletion in a patient presenting a complex phenotype that included pectoralis muscle hypoplasia. However, the contribution of genomic imbalances to PS remains largely unknown

Clinical Profile of Cardiac Involvement in Danon Disease: A Multicenter European Registry.

Background: The X-linked Danon disease manifests by severe cardiomyopathy, myopathy, and neuropsychiatric problems. We designed this registry to generate a comprehensive picture of clinical presentations and outcome of patients with Danon disease in cardiomyopathy centers throughout Europe. Methods: Clinical and genetic data were collected in 16 cardiology centers from 8 European countries. Results: The cohort comprised 30 male and 27 female patients. The age at diagnosis was birth to 42 years in men and 2 to 65 in women. Cardiac involvement was observed in 96%. Extracardiac manifestations were prominent in men but not in women. Left ventricular (LV) hypertrophy was reported in 73% of male and 74% of female patients. LV systolic dysfunction was reported in 40% of men (who had LV ejection fraction, 34±11%) and 59% of women (LV ejection fraction, 28±13%). The risk of arrhythmia and heart failure was comparable among sexes. The age of first heart failure hospitalization was lower in men (18±6 versus 28±17 years; P<0.003). Heart failure was the leading cause of death (10 of 17; 59%), and LV systolic dysfunction predicted an adverse outcome. Eight men and 8 women (28%) underwent heart transplantation or received an LV assist device. Our cohort suggests better prognosis of female compared with male heart transplant recipients. Conclusions: Danon disease presents earlier in men than in women and runs a malignant course in both sexes, due to cardiac complications. Cardiomyopathy features, heart failure and arrhythmia, are similar among the sexes. Clinical diagnosis and management is extremely challenging in women due to phenotypic diversity and the absence of extracardiac manifestations.pre-print507 K

The relationship between maximal left ventricular wall thickness and sudden cardiac death in childhood onset hypertrophic cardiomyopathy

Background: Maximal left ventricular wall thickness (MLVWT) is a risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). In adults, the severity of left ventricular hypertrophy has a nonlinear relationship with SCD, but it is not known whether the same complex relationship is seen in childhood. The aim of this study was to describe the relationship between left ventricular hypertrophy and SCD risk in a large international pediatric HCM cohort. Methods: The study cohort comprised 1075 children (mean age, 10.2 years [±4.4]) diagnosed with HCM (1–16 years) from the International Paediatric Hypertrophic Cardiomyopathy Consortium. Anonymized, noninvasive clinical data were collected from baseline evaluation and follow-up, and 5-year estimated SCD risk was calculated (HCM Risk-Kids). Results: MLVWT Z score was <10 in 598 (58.1%), ≥10 to <20 in 334 (31.1%), and ≥20 in 143 (13.3%). Higher MLVWT Z scores were associated with heart failure symptoms, unexplained syncope, left ventricular outflow tract obstruction, left atrial dilatation, and nonsustained ventricular tachycardia. One hundred twenty-two patients (71.3%) with MLVWT Z score ≥20 had coexisting risk factors for SCD. Over a median follow-up of 4.9 years (interquartile range, 2.3–9.3), 115 (10.7%) had an SCD event. Freedom from SCD event at 5 years for those with MLVWT Z scores <10, ≥10 to <20, and ≥20 was 95.6%, 87.4%, and 86.0, respectively. The estimated SCD risk at 5 years had a nonlinear, inverted U-shaped relationship with MLVWT Z score, peaking at Z score +23. The presence of coexisting risk factors had a summative effect on risk. Conclusions: In children with HCM, an inverted U-shaped relationship exists between left ventricular hypertrophy and estimated SCD risk. The presence of additional risk factors has a summative effect on risk. While MLVWT is important for risk stratification, it should not be used either as a binary variable or in isolation to guide implantable cardioverter defibrillator implantation decisions in children with HCM

Clinical Features and Natural History of Preadolescent Nonsyndromic Hypertrophic Cardiomyopathy

BACKGROUND Up to one-half of childhood sarcomeric hypertrophic cardiomyopathy (HCM) presents before the age of 12 years, but this patient group has not been systematically characterized. OBJECTIVES The aim of this study was to describe the clinical presentation and natural history of patients presenting with nonsyndromic HCM before the age of 12 years. METHODS Data from the International Paediatric Hypertrophic Cardiomyopathy Consortium on 639 children diagnosed with HCM younger than 12 years were collected and compared with those from 568 children diagnosed between 12 and 16 years. RESULTS At baseline, 339 patients (53.6%) had family histories of HCM, 132 (20.9%) had heart failure symptoms, and 250 (39.2%) were prescribed cardiac medications. The median maximal left ventricular wall thickness z-score was 8.7 (IQR: 5.3-14.4), and 145 patients (27.2%) had left ventricular outflow tract obstruction. Over a median follow-up period of 5.6 years (IQR: 2.3-10.0 years), 42 patients (6.6%) died, 21 (3.3%) underwent cardiac transplantation, and 69 (10.8%) had life-threatening arrhythmic events. Compared with those presenting after 12 years, a higher proportion of younger patients underwent myectomy (10.5% vs 7.2%; P = 0.045), but fewer received primary prevention implantable cardioverter-defibrillators (18.9% vs 30.1%; P = 0.041). The incidence of mortality or life-threatening arrhythmic events did not differ, but events occurred at a younger age. CONCLUSIONS Early-onset childhood HCM is associated with a comparable symptom burden and cardiac phenotype as in patients presenting later in childhood. Long-term outcomes including mortality did not differ by age of presentation, but patients presenting at younger than 12 years experienced adverse events at younger ages. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.Peer reviewe