Molecular autopsy and clinical family screening in a case of sudden cardiac death reveals ACTN2 mutation related to hypertrophic/dilated cardiomyopathy and a novel LZTR1 variant associated with Noonan syndrome.

BACKGROUND: Genetic cardiac diseases are the main trigger of sudden cardiac death (SCD) in young adults. Hypertrophic cardiomyopathy (HCM) is the most prevalent cardiomyopathy and accounts for 0.5 to 1% of SCD cases per year. METHODS: Herein, we report a family with a marked history of SCD focusing on one SCD young adult case and one pediatric case with HCM. RESULTS: For the deceased young adult, postmortem whole-exome sequencing (WES) revealed a missense variant in the ACTN2 gene: c.355G > A; p.(Ala119Thr) confirming the mixed hypertrophic/dilated cardiomyopathy phenotype detected in the autopsy. For the pediatric case, WES allowed us the identification of a novel frameshift variant in the LZTR1 gene: c.1745delT; p.(Val582Glyfs*10) which confirms a clinical suspicion of HCM related to Noonan syndrome. CONCLUSION: The present study adds further evidence on the pathogenicity of ACTN2: p. Ala119Thr variant in SCD and expands the mutational spectrum of the LZTR1 gene related to Noonan syndrome.

Novel ALPK3 mutation in a Tunisian patient with pediatric cardiomyopathy and facio-thoraco-skeletal features.

Pediatric cardiomyopathy is a complex disease with clinical and genetic heterogeneity. Recently, the ALPK3 gene was described as a new hereditary cardiomyopathy gene underlying pediatric cardiomyopathies. Only eight patients carrying mutations in ALPK3 have been reported to date. Here, we report a 3-year-old male patient with both hypertrophic and dilated cardiomyopathy. The patient presented dysmorphic features and skeletal deformities of hands and feet, pectus excavatum, and cleft palate. The genetic investigation was performed by whole-exome sequencing in the patient and his parents. We identified a novel homozygous mutation in ALPK3 (c.1531_1532delAA; p.Lys511Argfs*12). Our work extends the phenotypic spectrum of the ALPK3-associated cardiomyopathy by reporting additional clinical features. This is the first study of a Tunisian patient with mutation in the ALPK3 gene. In conclusion, ALPK3 should be included in the list of genes to be considered in genetic studies for patients affected with pediatric syndromic cardiomyopathy.

Giant aortic arch aneurysm complicating Kawasaki's disease.

Kawasaki disease (KD) is a common acute vasculitis in pediatric population that usually involves small- and middle-sized arteries, commonly coronary arteries. Although the incidence and natural course of coronary aneurysms after KD are well documented in studies, related reports on peripheral arterial and aortic aneurysms are scarce. We report the occurrence of a giant aortic aneurysm involving the horizontal part of aortic arch in a 28-month-old boy diagnosed with KD. This complication was managed by steroids therapy in the beginning. Because of mechanical complication and potential risk of rupture, surgery was undertaken.

[Circular shunt in the severe neonatal form of Ebstein's Anomaly. The prostaglandine infusion is it beneficial or harmful?] / Le shunt circulaire dans la forme néonatale sévère de la maladie d'Ebstein : effet bénéfique ou délétère des prostaglandines?

Ebstein's disease with functional pulmonary atresia is a severe neonatal presentation of Ebstein's anomaly where the therapeutic management is typically based on the prescription of prostaglandins. The circular shunt is a serious "hemodynamic" complication which is often undiagnosed leading to the discontinuation of prostaglandins. We report a severe neonatal form of Ebstein's anomaly with hemodynamic deterioration relatted to a circular shunt. The diagnosis of Ebstein's anomaly with functional pulmonary atresia was made prenatally at 36 weeks of pregnancy. The patient was born at 38 weeks of gestation by caesarean section. Postnatal ultrasound confirmed the diagnosis. Treatment with prostaglandins was originally created to maintain the vital ductus arteriosus patent. Despite this treatment, hemodynamic deterioration was observed. Ultrasound monitoring showed pictures for a circular shunt. Indeed, blood coming into the pulmonary artery by the wide ductus arteriosus, was "drawn" to the right ventricle and the right atrium due to tricuspid regurgitation and from there to the left heart via the fossa ovalis shunting right to left, when it was ejected into the aorta and the ductus arteriosus. Before this circular shunt, treatment with prostaglandin was discontinued and treatment to reduce pulmonary resistance was described. However, the patient died prior to initiation of treatment. The neonatal form of Ebstein's anomaly is a severe form that can be complicated by a circular shunt. This hemodynamic phenomenon encourages early closure of the ductus arteriosus against indicating the prescription of prostaglandins.

[Results of surgical treatment of intracardiac total anomalous pulmonary venous return]. / Résultats du traitement chirurgical du retour veineux pulmonaire anormal total intracardiaque :à propos de 7 cas.

BACKGROUND: Total anomalous pulmonary venous return (TAPVR) has a rather low incidence (1-3%) of all congenital heart disease. Intracardiac TAPVR represent 25-30% of all TAPVR. AIM: To report our results and long-term follow-up of surgical management of intracardiac TAPVR. METHODS: Retrospective study of 7 patients with intra cardiac TAPVR treated surgically between Mai 1992 and July 2007. RESULTS: The surgical technique has been an intra atrial procedure in all cases. We didn't report any early post-operative death. Early postoperative complications were principally pulmonary infections. We report one death at three months of follow-up caused by laryngeal stenosis. Late follow-up was good for all patients. CONCLUSION: Good result of surgical treatment of intracardiac TAPVR depends on early diagnosis and adequate surgical technique.

[Late reinterventions after repair of common arterial trunk]. / Les reinterventions tardives apres reparation du tronc arteriel commun.

BACKGROUND: The common arterial trunk is a heart disease in witch a unique arterial trunk, with a unique ventriculo-arterial valve, exits from the ventricular mass and supply directly the coronary, the aortic and also the pulmonary arterial circulations. Its anatomic repair is now possible but necessitates the use of conduit in pulmonary position. AIM: To evaluate the incidence and the causes of late reinterventions after repair of common arterial trunk. METHODS: We retrospectively study the outcome of 17 patients who underwent repair of common arterial trunk between January 1983 and December 2006. The 15 early survivors were followed during a median period of 7 years (range 10 months and 13 years). RESULTS: Nine reinterventions were necessary in 8 patients. Only one conduit reintervention was necessary in the 8 patients. Freedom from conduit reintervention was 73% at 5 years and 33% at 10 years. Three reinterventions were performed in 2 patients for severe truncal valve incompetence, including repair in 2 cases and replacement in one case. Freedom from truncal valve reintervention was 67% at 10 years. CONCLUSION: Late reinterventions are inevitable after repair of common arterial trunk. The most common reasons are conduit stenosis and truncal valve incompetence.

[Tetralogy of fallot with absent pulmonary valve]. / L'agenesie des valves pulmonaires avec communication interventriculaire.

BACKGROUND: Absent pulmonary valve with ventricular septal defect is a rare cardiac malformation. The aim of our study is to specify the anatomic characteristics and the clinical and echocardiographic features of this cardiac malformation and to discuss its management. METHODS: We report 8 cases of absent pulmonary valve with ventricular septal defected collected over a period of 24 years. The diagnosis was made during the first year of life in all cases in the presence of respiratory symptoms and/or cyanosis. It was confirmed by cardiac catheterization in 4 cases and echocardiography in 4 cases. RESULTS: Pulmonary vascular obstructive disease, related to aortopulmonary collateral vessels, was noted in one patient who died at the age of 20 years. One patient was lost to follow up and 6 patients were operated. Closure of the ventricular septal defect, widening of the pulmonary tract and insertion of a pulmonary valve were performed in the 6 cases. Reduction procedure of the pulmonary arteries was performed in 3 cases. One death related to early postoperative infective endocarditis was noted. At a mean follow up of 2 years, the 5 survivors are going well with no significant pulmonary stenosis. CONCLUSION: Although named "tetralogy of Fallot with absent pulmonary valve", absent pulmonary valve with ventricular septal defect is different from tetralogy of Fallot by aneurysmal dilatation of the pulmonary arteries which may compress the bronchial tree and lead to respiratory symptoms that can be severe with respiratory distress. Pulmonary arterioplasty eliminate airways obstruction and its results are satisfactory. The need for insertion of a pulmonary valve is debatable.

[Anatomic repair of transposition of the great arteries or arterial switch operation. Report of 62 cases]. / La reparation anatomique de la transposition des gros vaisseaux ou switch arteriel. A propos de 62 cas.

Between January 1990 and September 2003, 62 patients underwent anatomic repair of a transposition of the great arteries. Mean operative age is 40 days. Transposition of the great arteries was simple in 38 cases and associated to a large ventricular septal defect in 24 cases. 44 patients have had an atrial septostomy of Rashkind and 45 an infusion of prostaglandin E 1.5 patients with simple transposition of the great arteries have had left ventricular retraining before arteriel switch. In association to arterial switch, were performed closure of ventricular septal defect in 24 cases, cure of coarctation of the aorta in 4 cases and cure of an abnormal partial pulmonary venous return in 1 case. Early mortality was 6,45%. After a mean follow up of 3 years, one patient died suddenly (late mortality is 1.72%) and one patient had to have 2 reoperations. Results of anatomic repair are now excellent. Late mortality is essentially related to coronary complications so that a careful follow-up is mandatory.

[Atrial flutter in neonates and infants: diagnosis and treatment]. / Flutter auriculaire du nouveau-né et du nourisson: diagnostic & traitement.

Between 1995 and 2002, 5 patients with a mean age of 32 years have been treated for atrial flutter in the Department of Paediatric Cardiology at Hospital La Rabta. In all cases, diagnosis was established on surface electrocardiogram (12 leads. All patients had a normal heart. The 3 infants were in heart failure and In the 2 neonates, the arrhythmia was well tolerated despite a very fast ventricular rate. Reduction of the first episode of atrial flutter was possible by cardioversion in 3 patients, 2 of them had a good impregnation with Amiodarone. The two neonates died at 8th and 10th day of life. In the long term follow-up, on infant presented two recurrent episodes at 4 months x 2 years. Atrial flutter, when diagnosed in neonatal period is a rare but serious rhythm disturbance. The mechanism of activation of this rhythm disturbance remains unknown in the foetus, neonate and infant.