Abstract Body: Introduction: ACTA2 gene mutations are associated with Multisystemic Smooth Muscle Dysfunction Syndrome (MSMDS), an ultra-rare syndrome with premature morbidity and mortality. Infants with MSMDS commonly have patent ductus arteriosus (PDA) with atypical anatomy and congenital mydriasis, however, these PDA lesions have not been well characterized.
Hypothesis: Patients with MSMDS have large and complex PDA lesions that are addressed with varied surgical techniques.
Methods: Patients with ACTA2 arginine 179 mutations were enrolled in a prospective and retrospective natural history study from April 2024 to December 2025. Medical records were reviewed and data were extracted on PDA characteristics, surgical management, complications, and subsequent aortic interventions.
Results: Among 36 patients with ACTA2 arginine 179 mutations, 34 underwent PDA repair at 32 global centers. Two patients did not have available records. Median age at repair was 51 days (IQR 30-110 days) but was over 6 months for 5/34 patients (15%). Most PDAs were large and aortopulmonary window-like with friable, thin, or aneurysmal tissue. 28/34 patients (82%) had evidence of increased pulmonary vascular resistance. Only 2/34 patients (6%) had an ACTA2 mutation diagnosed before surgery. 15 patients (44%) underwent patch repair, 11 (32%) underwent ligation, and 5 (15%) underwent coarctation repair with end-to-end anastomosis at the time of PDA repair. None had primary device repair. The type of repair was unknown for 3 patients (9%). 13/34 patients (38%) had serious post-operative complications including PDA recanalization, pulmonary artery injury or stenosis, bronchial compression, aneurysmal PDA rupture, or stroke. Two patients (6%) required repeat PDA interventions with transcatheter closure devices. Of 5 patients with concomitant PDA and coarctation repair, 3 (60%) developed left bronchial compression versus none with PDA repair alone. 9/34 patients (26%) underwent subsequent aortic procedures at a median age of 14.4 years (IQR 13.5-18.5 years), most often aortic replacement.
Conclusions: Type B (window-like) PDA is a nearly universal finding in MSMDS and its treatment has a high complication rate. PDA alongside coarctation repair in MSMDS may be associated with left bronchial stenosis. Infants with PDA and congenital mydriasis should undergo early genetic testing, as preoperative diagnosis of MSMDS may prompt consideration of alternative surgical approaches and neuroprotective anesthesia.