Sagui Gavri

Conotruncal malformations and absent thymus due to a deleterious NKX2-6 mutation

Background Truncus arteriosus (TA) accounts for ∼1% of congenital heart defects. The aetiology of isolated TA is largely unknown but when occurring as part of a syndrome, it is mostly associated with chromosome 22q11 deletion. Vice versa, the most common congenital heart defects associated with chromosome 22q11 deletion are conotruncal malformations. In this study we investigated the cause of multiple conotruncal malformations accompanied by athymia in a consanguineous family. Methods and results Whole exome analysis revealed a homozygous deleterious mutation in the NKX2-6 gene. Conclusions NKX2-6 encodes a homeobox-containing protein which is expressed in mouse embryo at E8.0-E9.5 at the caudal pharyngeal arches and the outflow tract. A single missense mutation was previously implicated in the aetiology of familial isolated TA; however, null mice are entirely normal. The clear phenotype associated with a homozygous deleterious mutation in the present report, falls well within the spectrum of the cardiac defects seen in DiGeorge syndrome, is in agreement with NKX2-6 downstream location in the TBX1 signalling pathway and confirms NKX2-6 role in human cardiogenesis.

Intracardiac Echogenic Foci Have No Hemodynamic Significance in the Fetus

Intracardiac echogenic foci (ECFs), probably representing microcalcifications of the papillary muscles, are a common finding in fetal ultrasonic screening examinations. Their significance is unclear, and their value as markers for chromosomal anomalies is debatable. It also is unknown whether ECFs predict abnormal cardiac performance. This prospective study analyzed and compared the systolic and diastolic properties of the heart in 28 fetuses with ECFs and 70 fetuses without ECFs using both conventional and novel myocardial deformation methods. The findings suggest that left-sided ECFs do not predict depressed left- or right-side systolic or diastolic properties in the fetus. A longitudinal study that would follow ECF fetuses into their childhood is warranted to confirm the findings of this study.

Response to Letter Regarding Article, “Early Diagnosis and Treatment of Atrioventricular Block in the Fetus Exposed to Maternal Anti-SSA/ Ro-SSB/La Antibodies: A Prospective, Observational, Fetal Kinetocardiogram-Based Study”

We thank Guettrot-Imbert et al for their comments. They question whether all cases of first-degree atrioventricular block (AVB) were necessarily pathological and in need of treatment. They also question our 8.6% incidence of first-degree AVB versus the 1% to 2% rate described elsewhere. As emphasized in our article, our sole objective was to show the use of tissue velocity imaging–derived atrioventricular conduction measurement in this specific population, not to assess the efficacy of dexamethasone in anti-SSA/Ro- and/or anti-SSB/La-exposed fetuses. We agree that a blinded control study should be carefully designed for this purpose, although this …

Tetralogy of Fallot with Pulmonic Atresia with Cyclic Occlusion of an Associated Aortic Sinus of Valsalva–Pulmonary Artery Window

A first case of an unusual aortopulmonary window with tetralogy of Fallot associated with pulmonary atresia is presented. The aortopulmonary window was at the aortic sinus of Valsalva. The left aortic leaflet prevented pulmonary hypertension by occluding the window in systole.

OC162: Fetal kinetocardiogram for early detection and treatment of first‐degree AV block in fetuses exposed to maternal autoantibodies—a prospective study

the presence of a supernumerary vessel to the left of the pulmonary trunk in the 3-vessel view, a ‘cyst’ at the lateral wall of the left atrium or a dilated coronary sinus in the 4-chamber view. A meticulous inspection of the fetal anatomy was performed for detection of associated anomalies. Postnatal follow-up was available for all surviving patients. Prenatal diagnosis was confirmed by neonatal echocardiography or at autopsy. Results: Of 1155 cardiac referrals, 231 had a CHD (20%). A PLSVC was detected in 15 fetuses (1.2% of population at risk for CHD; 4.3% of fetuses with CHD). In 5 cases PLSVC had no associated condition. In 10 cases it was associated with CHD (6 with an isolated cardiac malformation, 3 with complex malformations syndromes and one with associated extracardiac anomalies). The most frequent CHD were ventricular septal defects and left ventricular outflow tract obstructions. The outcome of PLSVC was determined solely by the associated conditions. All cases with isolated PLSVC or associated correctable extracardiac malformations were alive and well at birth or after surgery. Conclusions: PLSVC is easily recognised on standard cardiac screening. Its detection in fetal life has to be followed by a meticulous inspection of fetal anatomy for its frequent association with cardiac/extracardiac malformations that determine the outcome. Isolated PLSVC is a benign vascular anomaly and may not affect the outcome.