Trichorhinophalangeal syndrome (TRPS) is a genetic disorder that may pose anesthetic challenges. We present a case of airway management for urgent surgery in a 56-year-old female with TRPS and difficult airway (macroglossia, narrow glottic opening, and hypoplastic epiglottis). Intubation was successful with video laryngoscopy using a size 2.5 pediatric blade and size 5.0 endotracheal tube. During emergence, she experienced bronchospasm and persistent urosepsis, necessitating intensive care unit (ICU) admission. Her pulmonary reserve was hindered by a Morgagni hernia causing lung compression. Our case demonstrates challenges in TRPS including challenging airway, decreased pulmonary reserve, and joint laxity introducing potential for spinal cord injury.