Introduction Early diagnosis of pediatric syndromes that are rare and involve multiple systems can be challenging. Rapid onset obesity, hypoventilation, hypothalamic dysfunction, and autonomic dysregulation characterizes ROHHAD syndrome which, if undiagnosed, can lead to potentially harmful outcomes including deferring radiological workup for a neural crest tumor (which has an over 50% association) and cardiopulmonary arrest. Report of case(s) A 10-year-old female with a history of obesity, precocious puberty, recurrent hypothermia, recurrent sodium derangements, bilateral ptosis, seizure disorder, and GERD initially presented to sleep clinic as a 4-year-old in 2017 when she recently began snoring with excessive daytime sleepiness as a result of rapid onset of weight gain. BMI at that time was 99th percentile and Epworth was 11. An in-lab polysomnography revealed severe OSA with AHI 26.4 events/hour; nocturnal hypoxemia with TS90 27% and O2 nadir 70%; and sleep related hypoventilation based on elevated pCO2 on end-tidal capnometry. Patient underwent adenotonsillectomy, revision adenoidectomy, and was started on CPAP before transitioning to BiPAP over the span of the next several years with serial polysomnographies ultimately showing significant improvement of sleep apnea with AHI 5.4 events/hour. Sleep-related hypoventilation, however, remained persistent with blood gases showing pCO2 as high as 89. PHOX2B gene testing was negative and secondary causes of hypoventilation were ruled out. During this time, she was also followed by Endocrinology for suspected hypothalamic dysfunction resulting in precocious puberty, deceleration of growth rate, sodium derangements. Autonomic dysfunction was also suspected due to recurrent hypothermia including a recent admission for Temperature < 95F and ophthalmologic abnormalities including bilateral ptosis. At a multidisciplinary care conference, a working diagnosis of ROHHAD syndrome was made based on the rapid onset of obesity, hypoventilation on sleep studies and CBGs, hypothalamic dysfunction, and autonomic degeneration. Workup for neural crest tumor with MRI chest and abdomen unremarkable. Outside academic consultation was sought for management which recommended shared decision-making regarding steroids, immunosuppressive therapy (eg rituximab, cyclophosphamide), and IVIG. Conclusion For ROHHAD syndrome, there are very few documented cases in the United States and there is no known laboratory marker; diagnosis remains clinical and takes multidisciplinary collaboration, education, and a high degree of suspicion. Support (if any)

Introduction Pediatric central sleep apnea (CSA) rarely initially presents in adolescent age groups, being more commonly diagnosed in infants. CSA may result from a multitude of neurological insults, such as stroke and brain masses. It may also less often present in metabolic and non-ischemic thrombotic disorders. Report of case(s) A 12-year-old female with history of global developmental delay of unclear etiology, chronic headaches, insulin resistance, and early morning tremors was referred for initial evaluation of possible narcolepsy. Severe daytime sleepiness had acutely worsened over the previous month. She was unable to stay awake during school, despite sleeping 13 hours per 24 hours. Central hypersomnia was suspected and polysomnogram with MSLT was scheduled. The patient presented to the Emergency Department 10 days later for worsening headaches and new oral aversion with 12-pound weight loss. Examination showed ataxic gait and dysarthria. Brain MRI revealed non-occlusive cerebral sinus venous thrombosis (CSVT) involving the superior sagittal sinus, right transverse sinus, right sigmoid sinus, right jugular bulb/vein, and cortical veins overlying both cerebral hemispheres with no stroke. Anticoagulation with enoxaparin was initiated and thrombophilia work-up commenced. Polysomnogram demonstrated a central AHI of 49.9/hr with significant periodic breathing and no obstructive sleep apnea. Oxygen titration sleep study failed to significantly improve CSA and BPAP was initiated. Thrombophilia work-up revealed severe hyperhomocysteinemia. Genetic analysis was consistent with autosomal recessive severe methylenetetrahydrofolate reductase (MTHFR) deficiency. The patient was begun on metabolic treatment with betaine, pyridoxine, hydroxocobalamin, and vitamin C, and transitioned to oral rivaroxaban. At 4 months, blood levels had normalized, and MRI demonstrated resolution of CSVT. Family endorsed BPAP compliance and complete resolution of all sleep symptoms. In addition, there was significant improvement in cognition, interpersonal skills, and abstract thought. Follow up polysomnogram 10 months after presentation demonstrated no CSA nor periodic breathing. Conclusion To our knowledge, this is the first report of MTHFR deficiency and CSVT resulting in severe CSA. While it is difficult to ascertain which entity ultimately caused the CSA, MTHFR deficiency can produce significant neurologic impairment through white matter disease and defective myelination, while CSVT can provoke venous hypertension, venous stasis, or hypoxia. Support (if any)

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Introduction Patent foramen ovale (PFO) in adults often remains asymptomatic until clinical manifestations such as cryptogenic stroke, migraine headache, air embolism, hypoxemia, or platypnea-orthodeoxia syndrome occur. In this case, prior workup of cryptogenic stroke failed to identify a PFO that was diagnosed after further investigation of polycythemia which revealed nocturnal hypoxemia on polysomnogram. Report of Cases: A 60-year-old male with history of recurrent venous thromboembolic events (VTE), secondary polycythemia, and cryptogenic strokes was referred for a polysomnogram during the evaluation of polycythemia. Over the span of six years, he had multiple cryptogenic strokes and VTEs in the setting of polycythemia and normal hypercoagulability labs. Further evaluation suggested secondary polycythemia after serum erythropoietin and JAK2 mutation testing were negative. The patient was a never smoker without evidence of malignancy or renal disease leading to suspicion that his polycythemia was due to hypoxemia despite normal oxygen saturations during point of care evaluations. He frequently reported shortness of breath during appointments. During a polysomnogram, the patient was found to have a total apnea-hypopnea index of fewer than 5 events per hour but demonstrated hypoxemia with 49.7% of total sleep time spent below an oxygen saturation of 90%. He was referred to pulmonology for further evaluation that showed normal resting oxygen saturation, no desaturation on a six-minute walk test, mild restrictive defect on pulmonary function testing, and a normal chest computed tomography with angiography. Prior transthoracic echocardiogram had demonstrated an atrial septal aneurysm without communication between the atrial chambers. No evidence suggestive of a right-to-left shunt was found on lateral imaging of the brain during a ventilation-perfusion scan. Further evaluation of the aneurysmal atrial septum on transesophageal echocardiogram with an agitated saline bubby study demonstrated a patent foramen ovale with a right-to-left shunt. In the setting of hypoxia leading to secondary polycythemia, the patient was scheduled for PFO closure. Conclusion Hypoxemia out of proportion to sleep-disordered breathing on polysomnogram should prompt further evaluation. Despite multiple prior strokes, our patient’s PFO had gone undiagnosed until polycythemia prompted a polysomnogram that demonstrated isolated nocturnal hypoxemia and prompted a further workup. Clinically significant hypoxemia is an indication for PFO closure. Support (If Any)

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