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Background: CaM (calmodulin), encoded by 3 separate genes ( CALM1 , CALM2 , and CALM3 ), is a multifunctional Ca 2+ -binding protein involved in many signal transduction events including ion channel regulation. CaM variants may present with early-onset long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia, or sudden cardiac death. Most reported variants occurred de novo. We identified a novel CALM3 variant, p.Asn138Lys (N138K), in a 4-generation family segregating with LQTS. The aim of this study was to elucidate its pathogenicity and to compare it with that of p.D130G-CaM-a variant associated with a severe LQTS phenotype., Methods: We performed whole exome sequencing for a large, 4-generation family affected by LQTS. To assess the effect of the detected CALM3 variant, the intrinsic Ca 2+ -binding affinity was measured by stoichiometric Ca 2+ titrations and equilibrium titrations. L-type Ca 2+ and slow delayed rectifier potassium currents (I CaL and I Ks ) were recorded by whole-cell patch-clamp. Cav1.2 and Kv7.1 membrane expression were determined by optical fluorescence assays., Results: We identified 14 p.N138K-CaM carriers in a family where 2 sudden deaths occurred in children. Several members were only mildly affected compared with CaM-LQTS patients to date described in literature. The intrinsic Ca 2+ -binding affinity of the CaM C-terminal domain was 10-fold lower for p.N138K-CaM compared with wild-type-CaM. I CaL inactivation was slowed in cells expressing p.N138K-CaM but less than in p.D130G-CaM cells. Unexpectedly, a larger I Ks current density was observed in cells expressing p.N138K-CaM, but not for p.D130G-CaM, compared with wild-type-CaM., Conclusions: The p.N138K CALM3 variant impairs Ca 2+ -binding affinity of CaM and I CaL inactivation but potentiates I Ks . The variably expressed phenotype of this variant compared with previously published de novo LQTS-CaM variants is likely explained by a milder impairment of I CaL inactivation combined with I Ks augmentation.

Background: Branch pulmonary artery stenosis complicates the management of congenital heart diseases. Surgical branch pulmonary artery angioplasty is associated with a high reintervention rate. As an alternative, percutaneous or intraoperative branch pulmonary artery stents have been implanted to improve efficiency, but long-term evaluations are limited., Aim: To describe the long-term evolution of branch pulmonary artery stents., Methods: We conducted a retrospective cohort study at Tours University Hospital. All stents implanted by surgery or catheterization in branch pulmonary arteries with a minimum follow-up of 12 months and at least one catheterization control were included. The primary endpoint combined cardiovascular mortality, surgical or percutaneous reintervention for stent complication or new stent implantation., Results: Between 2007 and 2017, 76 stents in 51 patients were included (62 stents implanted by surgery, 14 by catheterization). At implantation, the patients' mean age and weight were 4.7years (interquartile range 4.2years) and 17.3kg (interquartile range 11.0kg), respectively. Mean branch pulmonary artery minimum diameter was 4.1±2.1mm (mean Z-score-4.9±2.9), and mean initial stent diameter was 9.1±3.1mm. During a follow-up of 5.3years (range 0-11.2 years), freedom from primary endpoint was 86.8% (95% confidence interval 79.6-94.8%) at 1 year, 71.5% (95% confidence interval 61.9-82.7%) at 5years and 69.6% (95% confidence interval 59.6-81.2%) at 10 years. We did not identify any factors associated with major adverse cardiovascular events. Among stents without major adverse cardiovascular events, the mean branch pulmonary artery diameter Z-score at last evaluation had increased by +4.8±3.2 compared with the initial diameter (P<0.001). After stent implantation, a median of 2 re-expansions were performed for each stent (range 0-7)., Conclusions: Stent implantation should offer a good long-term solution for branch pulmonary artery stenosis, although iterative re-expansions are required., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Purpose: The distinction between physiologic (innocent) and pathologic (organic) heart murmurs is not always easy in routine practice, leading too often to unnecessary cardiology referrals and expensive investigations. We aimed to test the hypothesis that the complete disappearance of murmur on standing can exclude cardiac disease in children., Methods: From January 2014 to January 2015, we prospectively included 194 consecutive children aged 2 to 18 years who were referred for heart murmur evaluation to pediatric cardiologists at 2 French medical centers. Heart murmur characteristics while supine and then while standing were recorded, and an echo-cardiogram was performed., Results: Overall, 30 (15%) of the 194 children had a pathologic heart murmur as determined by an abnormal echocardiogram. Among the 100 children (51%) who had a murmur that was present while they were supine but completely disappeared when they stood up, only 2 had a pathologic murmur, and just 1 of them needed further evaluation. Complete disappearance of the heart murmur on standing therefore excluded a pathologic murmur with a high positive predictive value of 98% and specificity of 93%, albeit with a lower sensitivity of 60%., Conclusions: Disappearance of a heart murmur on standing is a reliable clinical tool for ruling out pathologic heart murmurs in children aged 2 years and older. This basic clinical assessment would avoid many unnecessary referrals to cardiologists., Competing Interests: Conflicts of interest: authors report none., (© 2017 Annals of Family Medicine, Inc.)

We report on the rare case of 7-year-old child presenting with frequent and apparently benign premature ventricular complexes (VPC) and left ventricular dysfunction. No structural disease of the heart was seen at cardiological evaluation. Eighteen months after the introduction of an antiarrhythmic treatment with low-dose bisoprolol, Holter monitoring showed 70,000 VPC in 24h with left ventricular function remaining decreased. Six months after increasing the dose of bisoprolol, the VPC were less frequent and left ventricular function was completely normalized. This case was characteristic of a cardiomyopathy induced by frequent premature ventricular contractions., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Heart murmurs are common in children and adolescents. Although most are innocent, an isolated heart murmur in asymptomatic children may be the sole finding indicating serious heart disease. Historical elements of familial heart disease, cardiovascular symptoms and a well-conducted medical examination can identify children with an increased risk of heart disease. The distinction between an innocent heart murmur and a pathologic heart murmur is not always easy for primary care physicians because most of them have little experience with auscultation searching for congenital heart malformation. Echocardiography provides a definitive diagnosis of heart disease but is not required in case of innocent murmur. Inappropriate pediatric cardiologist and echocardiographic referral leads to useless and expensive examinations, resulting in a work overload for pediatric cardiologists. The objective of this review is to provide the keys to differentiate innocent and pathologic murmurs, and to help physicians decide on the optimal diagnostic strategy., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Fetal intrapericardial teratomas are uncommon and usually benign. Their histology is the same as that of teratomas located elsewhere. They may cause death from non-immune hydrops fetalis and cardiac tamponade. We report a case that was successfully managed prenatally by placement of a pericardial amniotic shunt., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Unlabelled: The value of prenatal diagnosis of major congenital heart diseases (CHDs) has already been proved. In this study, we observed the evolution of the detection rate of CHDs and the quality of the diagnoses over a 15-year period in the Indre-et-Loire department of France., Method: Retrospective analysis of the quantitative and qualitative data of prenatal diagnosis between 2000 and 2005 (period 3) and comparison with studies conducted from 1991 to 1994 (period 1) and from 1995 to 1999 (period 2). The CHDs considered to be detectable are the major CHDs with neonatal symptoms. In order to analyze the quality of prenatal diagnosis, each diagnosis was classified as correct, false, or incomplete during period 3., Results: Period 3: 65.7% detectable CHDs were screened. Using period 1 criteria for prenatal diagnosis, the percentage of CHDs detected for periods 1, 2, and 3 was 43.2, 66.7, and 78%, respectively. Between periods 2 and 3, the detection rate increased from 52 to 74% for CHDs diagnosed with the visualization of the outflow tract. It increased from 63 to 71% for CHDs diagnosed with a four-chamber view. During period 3, diagnoses made by a pediatric cardiologist were correct and complete in 80% of cases. It was less than 25% otherwise., Conclusion: The improvement of prenatal diagnosis over time results from technological progress, the greater experience of ultrasonographers, and the systematic visualization of the outflow tract in addition to the four-chamber view. Despite the improvement in prenatal diagnosis, one-third of major CHDs were not screened before birth. Pediatricians still need to diagnose CHDs after birth., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Pompe disease is an autosomal recessive glycogen storage disorder caused by acid-alpha-glucosidase deficiency. The infantile form is usually fatal by 1 year of age in the absence of specific therapy. We report the cardiac follow-up of a 4-month-old boy treated with enzyme replacement therapy (ERT) for 8 months. The patient had no cardiac failure at the age of 1 year. Before starting ERT, ECG showed a shortened PR interval, with huge QRS complexes and biventricular hypertrophy; echocardiography demonstrated major hypertrophic cardiomyopathy. The QRS voltage (SV1+RV6) decreased from 13 to 2.9 mV after 32 weeks of ERT, suggesting a progressive reduction of cardiac hypertrophy and intracellular glycogen excess. The PR interval increased from 60 to 90 ms. A block of the right bundle branch appeared after 13 weeks of treatment. The indexed left ventricular mass decreased from 240 to 90 g/m2 after 30 weeks of ERT. The left ventricular ejection fraction decreased transitorily between the 5th and the 15 th weeks of treatment. In summary, ERT is an efficient therapeutic approach for the cardiomyopathy of infantile Pompe disease. However, the possible occurrence of a right bundle branch block and a transitory alteration in the ejection fraction highlight the importance of cardiac follow-up.

We describe two cases of congenital varicella. The first presented with cutaneous aplasia and scars; the second with skin abnormalities, limb atrophy, limb paresis, Horner's syndrome and liver calcifications: prognosis was poor in this case. After reviewing the published cases of congenital varicella, we advocate the use of varicella vaccine in seronegative women before pregnancy.

The aim of this study was to determine whether overexpression of stress proteins (SPs) could be a sensitive biomarker for cell injury due to exposure to low doses of volatile organic compounds (VOCs) such as benzene, ethylbenzene, toluene, xylene, and chlorinated derivatives (ClB). Sublethal and cytotoxic threshold concentrations of the VOCs were determined by studying the growth rate of normal (fibroblasts) or tumor-derived human cell lines (A549, HepG2) exposed for 4 days to VOCs. Changes in SP expression as a function of concentrations were investigated by Western blotting.VOC toxicity was found to be correlated with their degree of chlorination and their hydrophobicity. Cytotoxic threshold concentrations (no-observed effect concentration, NOEC) were found to be similar for the three cell lines. It was observed that using a mixture of VOCs, each of them at concentration below the NOEC, resulted in an actual toxicity to the cells. This finding reveals a synergistic effect and should be taken into account when assessing threshold risk and exposure limit values in the worker's environment when several pollutants may be present. HSP72 and HSP90 expression levels were not affected whereas GRP78 expression was increased by all the VOCs. Taking into account the specific molecular function of GRP78, it suggests that VOC exposure results in misfolded or underglycosylated protein accumulation in the endoplasmic reticulum. GRP78 overexpression was closely related to the magnitude of growth inhibition due to increasing concentrations of each VOC. The overexpression was found to be significant for concentrations 5 to 30 times higher than NOEC, indicating that, under our experimental conditions, GRP78 expression cannot be considered as a sensitive biomarker of exposure to environmental VOCs.

Unlabelled: The objective of this study is to report all of our experience of patent ductus arteriosus closure by interventional catheterisation, comparing two systems used successively: Rashkind umbrella and detachable coil., Method: Between January 1991 and July 2001, 72 patients underwent cardiac catheterisation in order to occlude patent ductus arteriosus (PDA). In 3 patients closure was not attempted (n = 1) or aborted (n = 2). The 69 patients in whom one or several prostheses were implanted are the object of this retrospective study. The patients were between 10 months and 18 years old (median 4 years), weighing between 6.7 and 54 kg (median 17 kg). The narrowest average angiographic diameter of the PDA was 2.2 mm (1 to 4 mm), type A in the Krichenko classification in 59 cases. The PDA was occluded by an umbrella in 29 patients (group 1), and from 1997 coils were used in 40 patients (group II). The medium term results were evaluated clinically and by colour doppler echocardiography., Results: The age, weight, size and type of PDA were similar in the 2 groups. Group 1: 28 patients were treated with a single umbrella and one patient received 2 umbrellas. Systemic embolisation occurred in one case. The average period of follow-up was from 4 years to 10 years (average 6.5 years). The rate of residual shunt at 24 h, 6 months, and 12 months was 43%, 43%, and 39% respectively. A second implant was necessary in 2 children after 7 months and 30 months. The spontaneous disappearance of residual shunt was observed in 8 patients after between 1 month and 54 months (average 33.5 months). A slight residual shunt persisted in 4 patients (13.7%), 4.5 to 8.5 years after placing one or two umbrellas. The patients with a residual shunt were younger: 37 months versus 73 months (p < 0.05). Group II: 34 patients received a single coil and 6 patients several coils. Two cases of embolic migration and two cases of haemolysis were observed. The follow-up extended from 4 months to 4.5 years (average 2.2 years). The rate of residual shunt at 24 h, 6 months, and 1 year respectively was 35%, 10.5%, and 3.3%. At 6 and 12 months this rate was significantly less in group I (p < 0.01). Implantation of supplementary coils was necessary in 2 children at 24 h and at 9 months. Spontaneous disappearance of residual shunt occurred in 10 children out of 14 with an average interval of 5.5 months. A weak residual shunt remained detectable in 2 patients (5%) at 6 months and 36 months., Conclusion: The rate of initial residual shunt is comparable using both techniques. Spontaneous disappearance of residual shunts was observed in the majority of cases, but with the detachable coils this outcome is faster and the final rate for residual shunt is very low.

Unlabelled: Metopic craniosynostosis may be an adverse effect of valproic acid exposed fetus., Cases: We report two infants with metopic craniosynostosis, born to mothers who were treated with valproic acid. In one case, a prenatal diagnosis was made. In the other case, only the male dizygotic twin was affected., Conclusion: Trigonocephaly may be a symptom of valproate embryofoetopathy detectable by antenatal ultrasound examination.

Unlabelled: Hepatic hemangioendothelioma can have a fatal outcome. After failure of classic therapies, and when surgery or arterial embolization are not possible, those benign tumours may benefit from interferon alpha treatment., Case Report: We report a case of a 14-month-old infant who presented with hepatic hemangiomatosis and cardiac failure. The disease can neither be controlled by steroids nor by radiotherapy associated with digitalo-diuretic treatment. Due to the important vascular volume of the tumour, neither surgical care nor arterial embolization were possible. Thus this infant was treated for ten months by interferon alpha. The evolution was favourable: cardiac failure, calcifications and volume of the angiomatosis were regressive., Conclusion: Interferon alpha treatment helps to control cardiac failure and the course of hepatic hemangioma in childhood.

Unlabelled: Drug administration during the last trimester of pregnancy may have adverse effects for the newborn., Case Report: A hemolytic anemia occurred during the first hours of life in a full-term neonate whose mother had taken nitrofurantoin during the last month of pregnancy., Conclusion: The immature enzymatic systems of the neonate are exposed to this adverse effect and justify the recommendation not to prescribe nitrofurantoin at the end of pregnancy.

Unlabelled: The association of aplasia cutis congenita and aortic coarctation could be a coincidence., Case Report: A neonate was born with an aplasia cutis congenita in the midline of the scalp. When she was two months old, an aortie coarctation was detected and surgically resected. Spontaneously, the scalp gradually cicatrized., Conclusion: A search for a candidate gene in this second reported case is mandated.

Background: Neonatal myoclonic encephalopathy is of lesional or metabolic origin; non ketotic hyperglycinemia is one of its causes., Case Report: A girl, born from consanguineous parents, died from myoclonic epileptic encephalopathy at the age of 3 months. Screening for metabolic disease was negative, except for increased levels of urine serotonin and 5-hydroxyindol-acetic in cerebrospinal fluid, blood and urine. Two sisters died with non ketotic hyperglycinemia, corpus callosum agenesis and clubfoot., Conclusion: Familial occurrence of non ketotic hyperglycinemia and early myoclonic epileptic encephalopathy is uncommon.

Unlabelled: Hypoglossia is a rare malformation that is not fatal, unlike otocephaly., Case Report: A neonate, born at 39 weeks of GA and dead at 5th day showed hypoglossia, dextrocardia, situs inversus and pituitary aplasia. Maternal hyperthermia was observed at 4 weeks gestation., Conclusion: This case is reminiscent of a community of syndrome with agnathia-holoprosencephaly and situs inversus. The responsibility of maternal hyperthermia is raised.

Background: Neonatal meningitis due to Alcaligenes xylosoxydans is exceptional; its diagnosis and treatment may be difficult., Case Report: A neonate born at 42 weeks of GA to a mother who worked as a nurse in an intensive care unit was admitted on day 2 for a severe infection. Her cerebrospinal (CSF) contained 1,970 white cell/mm3, polymorphonuclear in majority: direct examination failed to show any germ but the CSF and blood cultures were positive for Alcaligenes xylosoxydans, a strain that was resistant to the initially given antibiotics. The patient was given piperacillin, 300 mg/kg/d for 21 days and completely cured with a follow-up of 6 months., Conclusions: This case shows that lombar puncture can be necessary in evaluating early neonatal sepsis; it also shows usefulness of piperacillin in some cases.

Bergeyella zoohelcum is a Gram negative bacillus which can be found in several pathological localizations in man: leg abscesses, septicemia, meningitis. We observed a case of community-acquired pneumonia caused by Bergeyella zoohelcum. On history taking it was found that the patient was exposed to a dog which may have been the carrier of the Gram negative bacilli. The clinical course was long, one year, with persistent excavation.

The authors report a case of probable Haemophilus influenzae endocarditis in a 7 month-old infant with a bicuspid aortic valve. Precocity of the occurrence of endocarditis in such asymptomatic cardiac abnormality, scarcity of the suspected germ, and the observed mode of evolution are underlined. This case raises the problem of an endocardial involvement in an infant properly treated by adapted intravenous antibiotherapy. It can be concluded that regular clinical and echocardiographic examination is necessary for every case of severe Haemophilus influenzae infection.

In permanent malaria transmission area (Gabon), fluorescent malarial antibodies have been studied among a population of mothers new borns and children from 1 to 15 years old. A lack of transplacental transfer of antibodies among african pairs "cord-mother" is noticed and in negative correlation with total mother IgG level. The antibodies rapidly increase from 1-2 years old still 9. Chimioprophylaxis does'nt modified for a long time the development of the FAT malarial antibodies.

Prenatal diagnosis: The authors present a personal case of triose-phosphate-isomerase deficiency. Clinically the deficiency associates a constitutional non spherocytic anemia, paroxystic and precocius, and neuromuscular symptoms (axial hypotonia and limb palsies). A diaphragmatic paralysis may complicate the syndrome. Infections are frequent. Survival rarely goes beyond 5 years of age. Biochemical exams show the ubiquity of the deficiency. The physiopathology remains obscure. The TPI deficiency is heritable (autosomal recessive transmission). The gene has been mapped on the short arm of the chromosome 12. Prenatal diagnosis is possible.

It appears that a constant-speed infusion of isoproterinol is as reliable and sensitive a method of detecting coronary insufficiency as the exercise test. It is indicated when: - the exercise test is impossible or not submaximal; - there is disagreement between the clinical findings, which are suggestive, and ergometry, which is negative; - there is pure angina of effort arising spontaneously.

The authors report two cases of neonatal hemolytic anemia without methemoglobinemia secondary to intraamniotic injection of 10 mg of methylene blue. Evolution was favourable without exchange transfusion. This emphasizes the importance of searching for a toxic origin in case of neonatal hemolytic anemia without apparent cause.

Triose phosphate isomerase catalyses dihydroxyacetone phosphate to glyceraldehyde 3 phosphate isomerism. Its deficiency associates hemolytic anemia, neurologic abnormalities, relapsing infections and results in encephalopathy or early death. On the occasion of 2 new cases, we report one of the most important familial surveys as 93 subjects were studied, confirming the autosomal recessive transmission of the deficiency and the first results of antenatal diagnosis which could be performed in one of the families.

The management of fetal heterotopic tachycardias is reviewed from a cooperative study involving 23 cases treated by French Pediatric Cardiology Centers at Angers, Brest, Nantes, Rennes and Tours. There were 17 cases of supraventricular tachycardia (SVT), 5 of flutter and 1 of atrial tachycardia. Seventeen mothers were given an antiarrythmic treatment. They all received Digoxin by mouth, with either Propranolol in 2 cases, Sotalol and Verapamil in one case each. In 5 cases 2 or more other drugs were associated. There was a good in utero response in 12 cases. Among the 23 patients, 5 died, all with hydrops fetalis at the time of diagnosis of SVT. Finally 2 newborns were successfully treated at the time of delivery by a direct puncture of the umbilical cord.