In conclusion, we present the case of a 23-month-old boy with severe recurrent respiratory exacerbations associated with Rhinovirus infection. Thorough testing ruled out known risk factors such as congenital anomalies, immune deficiency or coinfections. A genetic analysis was performed, which failed to determine the presence of known genetic determinants of human RV susceptibility. There are few studies regarding the possible genetic mutations which increase the risk of severe respiratory exacerbations and respiratory failure secondary to viral infections, especially those involving human RV. A deeper understanding of these mutations would improve our knowledge and help identify at-risk patients with similar phenotypes to our case.