Neonatal repair of total anomalous pulmonary venous connection accompanied by unilateral lung agenesis and Goldenhar syndrome: a case report

Background Total anomalous pulmonary venous connection accompanied by unilateral lung agenesis and Goldenhar syndrome is extremely rare. Case presentation We present a case of total anomalous pulmonary venous connection accompanied by unilateral lung agenesis and Goldenhar syndrome in a patient who was diagnosed based on transthoracic echocardiography and computed tomography. We observed complete absence of the lung, the bronchial tree, and vascular structures on the right side, with abnormal drainage of the left pulmonary veins into the innominate vein. The patient showed clear clinical evidence of pulmonary venous obstruction and underwent surgery 3 days after birth. The pulmonary venous chamber containing the vertical vein was anastomosed to the left atrium using 7–0 PDS running sutures via a median sternotomy. Echocardiography and computed tomography performed 1 year postoperatively revealed no pulmonary venous obstruction. Conclusion We report a rare case of total anomalous pulmonary venous connection accompanied by unilateral lung agenesis and Goldenhar syndrome, which was successfully repaired 3 days after birth. A median sternotomy is a safe and effective approach for surgical repair of congenital heart disease with unilateral lung agenesis. Repair of the supra cardiac total anomalous pulmonary connection using the vertical vein is feasible in patients with a small pulmonary venous chamber.

Complete lung agenesis caused by complex genomic rearrangements with neo-TAD formation at the SHH locus

During human organogenesis, lung development is a timely and tightly regulated developmental process under the control of a large number of signaling molecules. Understanding how genetic variants can disturb normal lung development causing different lung malformations is a major goal for dissecting molecular mechanisms during embryogenesis. Here, through exome sequencing (ES), array CGH, genome sequencing (GS) and Hi-C, we aimed at elucidating the molecular basis of bilateral isolated lung agenesis in three fetuses born to a non-consanguineous family. We detected a complex genomic rearrangement containing duplicated, triplicated and deleted fragments involving the SHH locus in fetuses presenting complete agenesis of both lungs and near-complete agenesis of the trachea, diagnosed by ultrasound screening and confirmed at autopsy following termination. The rearrangement did not include SHH itself, but several regulatory elements for lung development, such as MACS1, a major SHH lung enhancer, and the neighboring genes MNX1 and NOM1. The rearrangement incorporated parts of two topologically associating domains (TADs) including their boundaries. Hi-C of cells from one of the affected fetuses showed the formation of two novel TADs each containing SHH enhancers and the MNX1 and NOM1 genes. Hi-C together with GS indicate that the new 3D conformation is likely causative for this condition by an inappropriate activation of MNX1 included in the neo-TADs by MACS1 enhancer, further highlighting the importance of the 3D chromatin conformation in human disease.

Late presentation of unilateral lung agenesis in adulthood

Background Pulmonary agenesis is a rare congenital anomaly with a reported prevalence of about 1 in 100,000 births. It may be bilateral or unilateral. Among the unilateral form, left lung agenesis is more common (70%); however, it is the right lung agenesis which carries a dismal prognosis due to the frequent association with a gamut of other congenital anomalies and greater degree of mediastinal shift leading to tracheo-bronchial and vascular distortion. The patients of unilateral pulmonary agenesis usually present in infancy or early childhood. Presentation in late adulthood as seen in our patient is rare. We present a case of left pulmonary agenesis that was diagnosed in 4th decade of life. Case presentation A 36-year-old male presented with gradually progressive exertional dyspnea of 1 month duration. Clinical examination revealed tachycardia and tachypnea. Chest radiograph showed opaque left hemithorax with ipsilateral mediastinal shift. Computed tomography clinched the diagnosis by demonstrating absence of left main bronchus, lung and left pulmonary artery with shift of heart, and great mediastinal vessels into left hemithorax. The patient was managed conservatively and discharged with attachment to out-patient department for regular follow-up. Conclusion Presentation of unilateral lung agenesis in late adulthood, as seen in the present case is extremely rare. This case report highlights that, a rare condition like unilateral pulmonary agenesis, should be considered in the list of differentials in an adult presenting with opaque hemithorax with ipsilateral mediastinal shift on radiography.

Neonatal Repair of Total Anomalous Pulmonary Venous Connection with Goldenhar Syndrome and Unilateral Lung Agenesis：A Case Report

Background: Total anomalous pulmonary venous connection with unilateral lung agenesis and Goldenhar syndrome is extremely rare and high mortality.Case presentation: We present a case of total anomalous pulmonary venous connection with unilateral lung agenesis and Goldenhar syndrome. It was diagnosed from Transthoracic echocardiography and enhanced Computed Tomography. Total absence of the lung, the bronchial tree, and vascular structures were detected on the right side, and the left pulmonary veins returned abnormally to the innominate vein. There was apparent indication of pulmonary venous obstruction, the operation was performed at 3 days after birth. The common pulmonary venous chamber with vertical vein and the left atrium was anastomosed using 7-0 PDS running sutures through a median sternotomy. Postoperative echocardiography and Computed Tomography 1 year after the surgery, between the common pulmonary venous chamber and the left atrium was no stenosis.Conclusion: A extremely rare case of total anomalous pulmonary venous connection with unilateral lung agenesis and Goldenhar syndrome successfully repaired at 3 day after birth was reported. Anastomosis between the common pulmonary venous chamber and the left atrium using the vertical vein is a reasonable choice in patient with small common pulmonary venous chamber.

Mosaic Trisomy 16 Associated with Left Lung Agenesis, Abnormal Left Arm, and Right Pulmonary Artery Stenosis: Expanding the Phenotype and Review of the Literature

Trisomy 16 is the most common autosomal trisomy found in spontaneous abortions with mosaic versions seen in survivors. However, surviving children have multiple congenital defects and are at risk of growth and developmental delay. We report an additional case of mosaic trisomy 16 diagnosed by amniocentesis and confirmed after birth. Our patient is the first documented case of living mosaic trisomy 16 with the malformation constellation of lung agenesis, left pulmonary artery agenesis, congenital heart defects, and ipsilateral radial ray and limb abnormalities, expanding the phenotype of this rare condition. Additionally, this individual's unique combination of lung and cardiac defects caused morbidities that were challenging to manage and complicated family counseling as well.

Right lung agenesis in a one-year-old Chihuahua

A one-year-old neutered male Chihuahua was referred for further investigations of spontaneous pneumothorax. Before referral, thoracocentesis and chest drain placement was performed. On presentation, the dog was dull and dyspnoeic displaying a restrictive respiratory pattern. Thoracic radiography and CT findings performed at the referral centre were consistent with right lung agenesis and pneumothorax. Retrospective review of the radiographs obtained at the referring practice identified right-sided mediastinal shift, separation of the cardiac silhouette from the sternum and overinflated left lung lobes. Neither free intrathoracic gas nor subcutaneous emphysema was identified. The initial images were suboptimally displayed resulting in artefactual ‘blackening’ of the lung parenchyma, necessitating digital manipulation to identify lung markings. The combination of mediastinal shift and separation of the cardiac silhouette from the sternum as a result of the right lung agenesis could potentially lead to a false impression of pneumothorax.