Spectrum Of Cardiac Anomalies Research Articles

Variants of SOS2 are a rare cause of Noonan syndrome with particular predisposition for lymphatic complications.

RASopathies are caused by variants in genes encoding components or modulators of the RAS/MAPK signaling pathway. Noonan syndrome is the most common entity among this group of disorders and is characterized by heart defects, short stature, variable developmental delay, and typical facial features. Heterozygous variants in SOS2, encoding a guanine nucleotide exchange factor for RAS, have recently been identified in patients with Noonan syndrome. The number of published cases with SOS2-related Noonan syndrome is still limited and little is known about genotype-phenotype correlations. We collected previously unpublished clinical and genotype data from 17 individuals carrying a disease-causing SOS2 variant. Most individuals had one of the previously reported dominant pathogenic variants; only four had novel changes at the established hotspots for variants that affect protein function. The overall phenotype of the 17 patients fits well into the spectrum of Noonan syndrome and is most similar to the phenotype observed in patients with SOS1-related Noonan syndrome, with ectodermal anomalies as common features and short stature and learning disabilities as relatively infrequent findings compared to the average Noonan syndrome phenotype. The spectrum of heart defects in SOS2-related Noonan syndrome was consistent with the known spectrum of cardiac anomalies in RASopathies, but no specific heart defect was particularly predominating. Notably, lymphatic anomalies were extraordinarily frequent, affecting more than half of the patients. We therefore conclude that SOS2-related Noonan syndrome is associated with a particularly high risk of lymphatic complications that may have a significant impact on morbidity and quality of life.

Unroofed Coronary Sinus Syndrome: An Easily Corrected Congenital Anomaly But More Diagnostic Suspicion Is Needed

Unroofed coronary sinus syndrome (URCSS) is a spectrum of cardiac anomalies in which part (partial type) or the entire common wall (complete type) between the coronary sinus (CS) and left atrium is absent. It is commonly associated with a persistent left superior vena cava (PLSVC). The PLSVC can even anomalously connect to the left atrium in complete type anomaly. URCSS has been reported to be associated with delayed diagnosis and life-threatening cerebral injury. The purpose of the present study was to review our experience with surgical correction of this often-concealed malformation and discuss methods for reducing diagnostic omission. Thirty-six patients with URCSS who underwent surgical treatment from 1998 to 2015 in our institution were enrolled in this retrospective analysis. The mean age of the patients was 21.8±20.9 years. Type I anomalies were found in 15 (41.7%) patients, type II in 4 (11.1%), type III in 6 (16.7%), and type IV in 11 (30.6%). A patient presenting with URCSS without other defects was identified in six (16.7%). One patient (2.8%) had a history of paradoxical embolisation. Twenty-five patients (69.4%) were diagnosed before surgery. Ten patients (27.8%) were diagnosed with URCSS intraoperatively. One patient (2.8%) was diagnosed with URCSS by follow-up echocardiography after device occlusion for atrial septal defect. Coronary sinus ostium dilation was the most important clue leading to partial type lesion disclosure intraoperatively. The anomalous PLSVC of 15 patients was repaired using roof tunnel technique in four (26.7%) cases, baffle redirection in eight (53.3%) cases, posterior left atrial wall plicating in two (13.3%) cases, and extracardiac bypass in one (6.7%) case. Postoperative complete atrioventricular block occurred in one patient (2.8%). One patient died postoperatively (2.8%). All patients are doing well after discharge from hospital. Diagnostic suspicion can contribute to lesion disclosure. Surgical correction has good long-term outcomes and low risks.

Unroofed coronary sinus and persistent left superior vena cava: A case report

The unroofed coronary sinus is a spectrum of cardiac anomalies in which part or all of the common wall between the coronary sinus and the left atrium is absent. Most cases are associated with anomalous systemic venous return, such as persistent left superior vena cava.The diagnosis of this lesion is important to the prognosis of the patient, but it is often difficult because of nonspecific clinical features.Here we report a case of a complete unroofed coronary sinus and persistent left superior vena cava discovered during a computed tomographic investigation for pulmonary hypertension.

A retrospective clinical study of incidence and spectrum of cardiac anomalies in non-syndromic subjects with cleft lip and palate

A retrospective clinical study of incidence and spectrum of cardiac anomalies in non-syndromic subjects with cleft lip and palate

The Spectrum of Cardiac Anomalies in Noonan Syndrome as a Result of Mutations in the PTPN11 Gene

Noonan syndrome is a clinically homogeneous but genetically heterogeneous condition. Type 1 Noonan syndrome is defined by the presence of a mutation in the PTPN11 gene, which is found in approximately 40% of the cases. Phenotype descriptions and cardiac defects from cohorts with Noonan syndrome were delineated in the "pregenomic era." We report the heart defects and links to gene dysfunction in cardiac development in a large cohort of patients with type 1 Noonan syndrome. This was a retrospective, multicenter study based on clinical history, pictures, and medical and cardiologic workup over time. Data were collected by referral geneticists. Mutation screening was performed by direct sequencing of exons 2, 3, 4, 7, 8, 12, and 13 and their intron-exon boundaries, which harbor 98% of identified mutations the PTPN11 gene. A PTPN11 gene mutation was identified in 104 (38.25%) of 274 patients with Noonan syndrome. Heart defect was present in 85%. The most prevalent congenital heart defects were pulmonary valve stenosis (60%), atrial septal defect, ostium secundum type (25%), and stenosis of the peripheral pulmonary arteries (in at least 15%). Pulmonary valve stenosis and atrial septal defect, ostium secundum type, were significantly associated with the identification of a mutation in the PTPN11 gene. Ventricular septal defect and most left-sided heart defects showed a trend toward overrepresentation in the group without a mutation. We compared our data with previous series and integrated the comprehension of molecular PTPN11 gene dysfunction in heart development.

Left-ventricular non-compaction in a patient with monosomy 1p36

We report on a new-born girl with left ventricular non-compaction (LVNC), dysmorphism and epilepsy. Array-CGH at 1 Mb resolution revealed a deletion of the terminal 4.6 to 5.9 Mb of the short arm of chromosome 1. Cardiac abnormalities such as dilated cardiomyopathy and structural cardiac defects are common findings in patients with monosomy 1p36. This is however the first report describing LVNC in association with the 1p36 deletion syndrome, broadening the spectrum of cardiac anomalies found in association with this syndrome.

Biventricular repair in the management of hypoplastic left heart syndrome.

Hypoplastic left heart syndrome is the term introduced by Noonan and Nadas1to describe a spectrum of cardiac anomalies characterized by varying degrees of significant underdevelopment of the left heart and aortic arch. These cardiac anomalies include mitral valvar disease, left ventricular hypoplasia, aortic stenosis at subvalvar, valvar, and supravalvar levels, hypoplasia of the ascending aorta and aortic arch, and aortic coarctation. Although descriptive, hypoplastic left heart syndrome suffers from being a very unspecific term, since it encompasses multiple degrees and combinations of abnormalities involving the left sided structures. In an attempt to provide gradings of severity, Kirklin and Barratt-Boyes2categorized these patients falling into the syndrome into four classes, according to whether obstruction was found at one, two, or more levels, or whether there is aortic atresia. Then, in 1998, Tchervenkov and colleagues3introduced the term hypoplastic left heart complex to describe a set of patients falling within the spectrum of hypoplasia of the left heart, but in the absence of intrinsic aortic or mitral valvar stenosis, this concept subsequently being endorsed by the International Committee established by the Society of Thoracic Surgeons, together with the European Association of Cardiothoracic Surgery, to rationalize the approach to nomenclature and databases.4The analysis offered by Tchervenkov et al.3showed that, in certain circumstances, there are potentially patients considered to have hypoplasia of the left heart who might be candidates for biventricular repair. If this is the case, then it is important to establish how this subset can be recognized, and how they are best treated.

Spectrum of Congenital Cardiac Anomalies Produced in Chick Embryos by Mechanical Interference with Cardiogenesis

Stage 19 to 20 white leghorn chick embryos were subjected to an operative manipulation in which a wire device was passed under the outflow tract of the cardiac tube, and allowed to remain in place from 24 to 60 hours. The embryos were then permitted to develop until hatching. Twenty-eight embryos, including eight sham operated controls, all of whom were normal, survived to at least the 18th embryonic day, and are included in this report. A spectrum of cardiac anomalies was produced as follows: group 1, widening of the left ventricular outflow tract unassociated with other defects; group 2, widening of the left ventricular outflow tract with a subaortic ventricular septal defect, 0.8 mm or less in its greatest dimension; group 3, a large ventricular septal defect, 1.5 mm or more in its greatest dimension, with varying degrees of abnormal position of the aorta, including "overriding" of the aorta, but with maintenance of continuity between the aortic and mitral valve annuli; group 4, the double outlet syndrome, in which both great vessels arise from the anatomic right ventricle with complete muscular separation between the aortic and mitral valves. In the time period studied, the double outlet syndrome represents the extreme of the continuum. However, it is possible that other forms of this spectrum exist, some perhaps incompatible with embryonic life, and that these may be produced by changing the experimental technique.