Multisystemic Smooth Muscle Dysfunction Syndrome:An Unusual Cause for a Gigantic PDA with Bilateral Mydriasis

Objective: A patent arterial duct (PDA) is a common lesion usually treated by interventional measures. Rarely the PDA requires surgical intervention in babies > 2 kg body weight. Surgical intervention may also be required in premature babies and in those patients where the PDA exceeds the diameter of the aorta.

Patient History: The patient (ex 36 weeks of gestation, birth weight 2,565 g) was referred to our center at the age of 4 weeks (2,590 g, 48 cm) for the treatment of a gigantic PDA. Pharmacologic PDA closure has failed before and there were clinical signs of heart failure with tachypnea and left heart failure including retrograde flow in the abdominal aorta and severe pulmonary hypertension. In addition there was a small ASD. Important additional clinical features were extremely wide pupils not reacting to light admission (mydriasis), microcephaly and feeding difficulties with pathologic signs of cholestasis (YGT 220 U/l, bilirubin max 21 mg/dl), a large gall bladder, a hypotonic urinary bladder with voiding difficulties and bilateral periventricular white matter lesions. Catheter investigation revealed a window-type PDA with a diameter of 6 mm and the adjacent aorta of 5 mm only. Interventional treatment was not feasible and surgical PDA ligation was performed using a modified ligation technique. The clinical course was complicated by pulmonary hypertension and the patient could be extubated 5 days after the procedure.

Genetic Counseling: Based on the typical clinical findings with maximal mydriasis and a gigantic PDA further focused genetic analysis revealed a ACTA2 mutation of the protein α-actin in the smooth muscle cells. Patients described with this genetic variation present with a syndrome characterized by ascending aortic aneurysms, large PDAs, cerebrovascular disease, periventricular white matter lesions, congenital mydriasis, hypotonic bladder, intestinal malrotation and hypoperistalsis and pulmonary hypertension associated vascular changes.

Conclusion: The characteristic findings of a gigantic PDA in combination with a bilateral mydriasis should lead to the presumed diagnosis of a the ACTA2 mutation with the clinical presentation of multisystemic smooth muscle dysfunction syndrome.