This report describes a preterm male infant with phenotypic features of mild facial dysmorphism, congenital abnormalities of the hands and feet, corneal clouding, hypertonia, bilateral sensorineural hearing loss, and bilateral ventriculomegaly. His clinical course was significant for severe cyanotic episodes associated with the advancement of feed volume. Microarray analysis identified a large constitutional de novo deletion of 7q21.3q31.1. This rare deletion has never been reported in a preterm infant, and the management of this patient will help offer clinical guidance for this genetic condition.