Splicing mutation in the fibrillin-1 gene associated with neonatal Marfan syndrome and severe pulmonary emphysema with tracheobronchomalacia

Neonatal Marfan syndrome is an autosomal-dominant connective tissue disease with unique clinical manifestations and mutations. We describe the clinical course of an infant with neonatal Marfan syndrome that had the novel IVS31-2A > G splice site mutation in fibrillin-1. This mutation affects the second base of the acceptor consensus splice site of intron 31, and probably leads to abnormal splicing events. The patient presented with respiratory distress and heart murmur in early neonatal life. Cardiac evaluation revealed pulmonic stenosis, atrioventricular regurgitation, and a dilated aortic root that were controlled by balloon dilatation of the pulmonic stenosis and medications for congestive heart failure. At age 3 months, he presented with severe respiratory distress caused by upper and lower airway obstruction. Imaging studies showed severe pulmonary emphysema, and a bronchoscopy demonstrated megatracheobronchomalacia, an unusual finding in this syndrome. Subsequently, the patient developed recurrent hyperinflation of the right and left lungs, with emphysematous changes and mediastinal shift. After discussing with his parents the grave prognosis for neonatal Marfan syndrome, he was discharged home with oxygen treatment and died at home at age 4.5 months. This case report demonstrates and discusses pulmonary involvement in neonatal Marfan syndrome and the difficult therapeutic challenges created by the severe cardiopulmonary abnormalities in this invariably fatal condition.