Frequency of 22q11 deletions in patients with conotruncal defects

AbstractObjectives. This study was designed to determine the frequency of 22q11 deletions in a large, prospectively ascertained sample of patients with conotruncal defects and to evaluate the deletion frequency when additional cardiac findings are also considered.Background. Chromosome 22q11 deletions are present in the majority of patients with DiGeorge, velocardiofacial and conotruncal anomaly face syndromes in which conotruncal defects are a cardinal feature. Previous studies suggest that a substantial number of patients with congenital heart disease have a 22q11 deletion.Methods. Two hundred fifty-one patients with conotruncal defects were prospectively enrolled into the study and screened for the presence of a 22q11 deletion.Results. Deletions were found in 50.0% with interrupted aortic arch (IAA), 34.5% of patients with truncus arteriosus (TA), and 15.9% with tetralogy of Fallot (TOF). Two of 6 patients with a posterior malalignment type ventricular septal defect (PMVSD) and only 1 of 20 patients with double outlet right ventricle were found to have a 22q11 deletion. None of the 45 patients with transposition of the great arteries had a deletion. The frequency of 22q11 deletions was higher in patients with anomalies of the pulmonary arteries, aortic arch or its major branches as compared to patients with a normal left aortic arch regardless of intracardiac anatomy.Conclusions. A substantial proportion of patients with IAA, TA, TOF and PMVSD have a deletion of chromosome 22q11. Deletions are more common in patients with aortic arch or vessel anomalies. These results begin to define guidelines for deletion screening of patients with conotruncal defects

Clinical presentation of calmodulin mutations: the International Calmodulinopathy Registry

AIMS: Calmodulinopathy due to mutations in any of the three CALM genes (CALM1-3) causes life-threatening arrhythmia syndromes, especially in young individuals. The International Calmodulinopathy Registry (ICalmR) aims to define and link the increasing complexity of the clinical presentation to the underlying molecular mechanisms. METHODS AND RESULTS: The ICalmR is an international, collaborative, observational study, assembling and analysing clinical and genetic data on CALM-positive patients. The ICalmR has enrolled 140 subjects (median age 10.8 years [interquartile range 5-19]), 97 index cases and 43 family members. CALM-LQTS and CALM-CPVT are the prevalent phenotypes. Primary neurological manifestations, unrelated to post-anoxic sequelae, manifested in 20 patients. Calmodulinopathy remains associated with a high arrhythmic event rate (symptomatic patients, n = 103, 74%). However, compared with the original 2019 cohort, there was a reduced frequency and severity of all cardiac events (61% vs. 85%; P = .001) and sudden death (9% vs. 27%; P = .008). Data on therapy do not allow definitive recommendations. Cardiac structural abnormalities, either cardiomyopathy or congenital heart defects, are present in 30% of patients, mainly CALM-LQTS, and lethal cases of heart failure have occurred. The number of familial cases and of families with strikingly different phenotypes is increasing. CONCLUSION: Calmodulinopathy has pleiotropic presentations, from channelopathy to syndromic forms. Clinical severity ranges from the early onset of life-threatening arrhythmias to the absence of symptoms, and the percentage of milder and familial forms is increasing. There are no hard data to guide therapy, and current management includes pharmacological and surgical antiadrenergic interventions with sodium channel blockers often accompanied by an implantable cardioverter-defibrillator

Magnetocardiography-Guided Management of an Unusual Case of Isoimmune Complete Atrioventricular Block Complicated by Ventricular Tachycardia

A fetus who was diagnosed at 25 weeks of gestation with isoimmune AV block presented at 34 weeks with a precipitous fall in ventricular rate and periods of tachycardia. Magnetocardiography revealed the tachycardia to be ventricular. After delivery, nonsustained ventricular tachycardia continued. The baby then successfully paced, and at higher ventricular rates the tachycardia resolved. Five years later the child has normal ventricular function and is doing well

Myocardial tissue Doppler velocities in fetuses with hypoplastic left heart syndrome

Background : Tissue Doppler Imaging (TDI) is a sensitive index of myocardial function. Its role in the fetus has not been extensively evaluated. Objective: To compare myocardial tissue Doppler velocities in fetuses with hypoplastic left heart syndrome (HLHS) to those of normal fetuses (matched for gestational age.) Methods: Cross-sectional retrospective study conducted at 2 large perinatal centers (2003-2007). Fetuses with HLHS ( n = 13) were compared with normal fetuses ( n = 207) in 5 gestational age groups. TDI data included peak systolic (s′), peak early (e′), and late diastolic velocities (a′). Linear regression was used to compare TDI parameters in fetuses with HLHS to normal fetuses matched for gestational age. Results: Fetuses with HLHS had significantly reduced lateral tricuspid annular e′ as compared to normal fetuses. Both normal fetuses and those with HLHS had linear increase in TDI velocities with advancing gestational age. Conclusions: TDI velocities are abnormal in fetuses with HLHS. TDI can be useful in serial follow-up of cardiac function in fetuses with HLHS