Cerebro-costo-mandibular syndrome is characterized by severe micrognathia with glossoptosis, short to cleft soft palate, bell-shaped small thorax with gaps between the posterior ossified rib and anterior cartilaginous rib and postnatal growth and mental deficiency. We present the clinical course and the early aggressive treatment of a newborn diagnosed as cerebro-costo-mandibular syndrome. The management of the patients with this syndrome is important over the morbidity and mortality. Most babies died due to respiratory distress. Although brain anomalies are uncommon in cerebro-costo-mandibular syndrome, hypoxia may cause neurodevelopmental disorders. In this case report, we emphasize the importance of proper ventilation and feeding in patients with cerebro-costo-mandibular syndrome to maintain normal development. Multidisciplinary approach is essential in monitoring of these patients.