A 13‐mo girl was admitted to the pediatric intensive care unit for acute respiratory distress syndrome (ARDS). She presented to an ED with fever for 2 days and weakness. There she had a SpO2 of 59%, thus was intubated and transferred to our hospital. She was previously healthy except for an episode of apnea and “turning blue” at 5months during an upper respiratory tract infection. Her initial CXR was consistent with ARDS and a CT chest showed diffuse interstitial lung disease. An ECHO showed a small PFO, but normal function. A Respiratory Viral Panel was positive for parainfluenza 3. As her ARDS improved and sedation weaned, she became alert and vigorous. However she did not tolerate a ventilator wean. During attempts her PCO2 levels rose up to 144 torr without signs of respiratory distress or increased effort. She did not have ptosis or ophthalmoplegia. MRI brain showed an incidental finding of an old right cerebellar injury possibly due to infarct or germinal matrix hemorrhage in the in‐utero/neonatal period. Respiratory control disorder was suspected and blood was sent for a PHOX2B gene mutation to diagnose Congenital Central Hypoventilation Syndrome (CCHS). She was positive for PHOX2B gene mutation, 20/25 polyalanine repeat expansion mutation (PARM) genotype confirming CCHS. The patient received a tracheostomy for positive pressure ventilation. She continued to improve and 3 months later was discharged on a home ventilator.
Adequate ventilation is determined by respiratory load, ventilator muscle power, and central drive. If a patient cannot be weaned from a ventilator, all three components of respiratory balance must be explored. This patient did not have lasting lung disease from her parainfluenza 3 infection. As she recovered, her neurological examination normalized suggesting an absence of neuromuscular disease. With sprints off the ventilator she exhibited adequate diaphragmatic contraction, thus her high PCO2 levels could not be explained by ventilatory muscle failure. This led to an investigation for a decrease in her central drive.
Congenital Central Hypoventilation Syndrome (CCHS) or “Ondine’s Curse” is a rare disorder of the autonomic nervous system (ANS) that primarily manifests as profound hypoventilation during sleep. It is caused by a mutation in the PHOX2B gene that plays a crucial role in the development of the ANS. The need for ventilatory support and associated autonomic conditions are related to the genotype. The 20/25 PARM genotype is associated with a milder phenotype. Mild cases of CCHS may only present following sedation, anesthesia or severe respiratory infection, as seen in our patient. Patients may present in later infancy, or even adulthood. Since CCHS patients do not outgrow their disorder, they require life‐long assisted ventilation. Parents of patients with CCHS need to be tested for the PHOX2B mutation to determine the risk of CCHS in future children and their own risk of ANS disorders.
When unable to wean a child from a ventilator, hospitalists should explore all elements of respiratory balance and consider disorders of respiratory drive. Suspect CCHS in patients with persistent, unexplained hypoventilation following sedation or severe respiratory infection. PHOX 2B gene mutation is required for diagnosis of CCHS. Early diagnosis can lead to early intervention, thus optimizing outcomes.