Congenital heart defects and left ventricular non-compaction in males with loss-of-function variants in NONO.

BACKGROUND: The non-POU domain containing octamer-binding gene (NONO) is located on chromosome Xq13.1 and encodes a member of a small family of RNA-binding and DNA-binding proteins that perform a variety of tasks involved in RNA synthesis, transcriptional regulation and DNA repair. Loss-of-function variants in NONO have been described as a cause of intellectual disability in males but have not been described in association with congenital heart defects or cardiomyopathy. In this article, we seek to further define the phenotypic consequences of NONO depletion in human subjects. METHODS: We searched a clinical database of over 6000 individuals referred for exome sequencing and over 60 000 individuals referred for CNV analysis. RESULTS: We identified two males with atrial and ventricular septal defects, left ventricular non-compaction (LVNC), developmental delay and intellectual disability, who harboured de novo, loss-of-function variants in NONO. We also identified a male infant with developmental delay, congenital brain anomalies and severe LVNC requiring cardiac transplantation, who inherited a single-gene deletion of NONO from his asymptomatic mother. CONCLUSIONS: We conclude that in addition to global developmental delay and intellectual disability, males with loss-of-function variants in NONO may also be predisposed to developing congenital heart defects and LVNC with the penetrance of these cardiac-related problems being influenced by genetic, epigenetic, environmental or stochastic factors. Brain imaging of males with NONO deficiency may reveal structural defects with abnormalities of the corpus callosum being the most common. Although dysmorphic features vary between affected individuals, relative macrocephaly is a common feature.

Benign Structures Mimicking Right Atrial Masses on Prenatal Ultrasound.

Advances in imaging have resulted in more frequent reporting of primitive right atrial structures which can sometimes mimic cardiac tumors in prenatal ultrasound. Prominent crista terminalis and Chiari network are examples of these structures. We describe two cases of pregnant women referred to the fetal cardiology clinic for fetal echocardiography for right atrial masses seen on prenatal ultrasound suspicious of tuberous sclerosis. The first case subsequently diagnosed as crista terminalis and the second case as a prominent Chiari network. Postnatal ECHO confirmed the benign nature of these structures. It is important to differentiate tumors from prominent benign structures in the right atrium in fetal ECHO. The location and the similar echogenicity to the adjacent atrial tissue are clues for differentiation of these structures from atrial tumors.

High-sensitivity troponin T in preterm infants with a hemodynamically significant patent ductus arteriosus.

OBJECTIVE: To investigate if a hemodynamically significant patent ductus arteriosus (hsPDA) leads to elevated high-sensitivity troponin T (hsTnT) and NTproBNP levels in serum. STUDY DESIGN: Infants <34 weeks and <1500 g were prospectively enrolled, except those with major congenital or chromosomal anomalies. An echocardiogram (ECHO) was performed and hsTnT and NTproBNP were measured within 5 days of life and repeated after treatment of hsPDA. Clinical, ECHO, and hsTnT data were analyzed using Student t-test, two proportion z-test, and regression analysis. RESULTS: Seventy infants were enrolled. Infants in the hsPDA group had lower gestation and birth weight. Mean hsTnT and NTproBNP levels in the hsPDA group were higher compared to the group without an hsPDA, with levels being 251.54 vs 161.6 pg/ml, p < 0.01 for hsTnT and 18181.02 vs 3149.23 pg/ml, p < 0.001 for NTproBNP. CONCLUSION: HsPDA leads to increased hsTnT and NTproBNP levels in preterm infants without affecting cardiac function.

Coarctation of the Aorta as a Complication of Surgical Ligation of Patent Ductus Arteriosus in a Premature Infant.

Surgical ligation of a patent ductus arteriosus (PDA) is a commonly performed procedure. Complications are infrequent and most commonly include recurrent laryngeal nerve injury and rarely ligation of left pulmonary artery. We report a case of accidental ligation of the descending thoracic aorta leading to a clinically significant coarctation.

Absent pulmonary valve syndrome with left hemitruncus.

Absent pulmonary valve syndrome (APVS) is a rare congenital heart defect, usually associated with tetralogy of Fallot (TOF), although other associations have been described. A pregnant woman was referred to fetal echocardiography clinic from the Maternal Fetal Medicine department due to abnormal findings on routine antenatal ultrasound, showing a pulsatile cystic mass above the left atrium and a suspected TOF. A fetal echocardiogram confirmed the presence of TOF/APVS. The pulsatile cystic mass was the aneurysmally dilated main pulmonary artery. The exact origin of the left pulmonary artery (LPA) was not clearly established prenatally. A postnatal echocardiogram of the neonate showed an abnormal origin of the LPA from the ascending aorta (hemitruncus). The neonate subsequently underwent surgical repair with a good outcome. We present a novel case of a TOF/APVS associated with an abnormal origin of the LPA from the ascending aorta.