New Mutation in TGFBR2 in a Female Newborn with Aortic Rupture

Background: Mutations in the transforming growth factor β receptor (TGFBR) gene are associated with Loeys–Dietz syndrome (LDS). These mutations have been linked to heart and vessel malformations, bone and craniofacial deformities, skin and eye anomalies, and allergies.

Methods: A trio-based whole exome sequencing identified a novel heterozygous variation in the TGFBR2 gene, c.1472–3 C>A (NM_001024827.2), with uncertain clinical significance.

Results: Here, we report the case of a female newborn with a mutation in TGFBR2. The patient exhibited microcephaly and heterotaxy. The cardiac defect was a double outlet right ventricle (DORV) with an atrial septal defect (ASD) and a patent ductus arteriosus (PDA). Furthermore, a cervical aortic arch with a small middle part and a hemiazygos vein, as well as bilateral superior vena cava, was observed. The patient also exhibited extracardiac syndromes, including talipes, bilateral knee joint dislocation, a bone cleft palate, and convergent strabismus. The mother presented a mosaic with 15% of this mutation but without any symptoms. The delivery was performed in a prenatal center with adequate adaptation of the newborn. On the fourth day of life, the patient was transferred to our pediatric cardiology hospital. Due to a stable cardiac function under heart failure therapy, we decided to perform a corrective operation at 3 months of age, which included VSD closure, ASD closure, and PDA suture. The patient was discharged on the 14th day after the surgery with captopril due to elevated blood pressure. Eight weeks following the surgery, the patient presented an acute reduction in their general condition. The initial blood gas analysis indicated a pH of 6.8, a lactate level of 18 mmol/L, and a potassium level of 8.9 mmol/L, consistent with circulatory centralization. The X-ray revealed evidence of pleural effusion, necessitating drainage. Due to the occurrence of pulsatile bleeding, the procedure was terminated and the patient was transferred to our pediatric cardiology hospital. The CT scan revealed a covered rupture of a 5 × 4 × 4 cm pseudoaneurysm of the aortic arch, as well as compression of the left pulmonary artery and left main bronchus, a rightward shift of the mediastinum and trachea. Given the complexity of the anatomy and the difficulty of surgery or intervention, the consensus of the team was to end the treatment, which led to exitus.

Conclusion: This study presents a novel TGFBR2 heterozygous variant, that has not previously been considered pathological. TGFBR2 mutations are associated with Loeys–Dietz syndrome and thus with aortic rupture. But, there has never been a case of aortic rupture in infants.

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Artikel online veröffentlicht:
11. Februar 2025