What question did this study set out to answer?

To explore the association between a PHOX2B mutation and sustained diurnal hypertension in a patient with congenital central hypoventilation syndrome (CCHS).

March 21, 2026Open Access

PHOX2B Tyr14Ter Mutation Might Be Associated with Sustained Diurnal Hypertension: Case Report and Review of the Literature

Key Points

To explore the association between a PHOX2B mutation and sustained diurnal hypertension in a patient with congenital central hypoventilation syndrome (CCHS).
Reported case of a 16-month-old male with CCHS after RSV infection
Utilized genetic testing for PHOX2B mutation identification
Conducted transcutaneous capnography and nocturnal pulse oximetry for diagnosis
Monitored blood pressure and assessed for hypertension treatment
Identified a de novo nonsense mutation in PHOX2B (p.Tyr14Ter)
Observed severe hypercapnia (PaCO2 70 mmHg) requiring invasive ventilation
Documented early-onset systemic hypertension necessitating antihypertensive therapy
Patient discharged on nocturnal non-invasive ventilation and enrolled in rehabilitation program

Abstract

Introduction: Congenital central hypoventilation syndrome (CCHS) is a rare disorder characterized by an impaired ventilatory response to hypercapnia and hypoxia, particularly during sleep, and frequently associated with autonomic dysfunction. It is caused by pathogenic variants in the PHOX2B gene. Although CCHS is typically diagnosed in the neonatal period, milder forms may present later in infancy or childhood, often triggered by respiratory infections. Case presentation: We report the case of 16-month-old male diagnosed with CCHS following an episode of hypoxemic–hypercapnic respiratory failure during respiratory syncytial virus (RSV) infection. His medical history included neonatal respiratory distress requiring oxygen therapy and recurrent wheezing. At 15 months, he developed acute respiratory distress with severe hypercapnia (PaCO2 70 mmHg), requiring admission to the Pediatric Intensive Care Unit and invasive mechanical ventilation. Persistent sleep-related hypercapnia and hypoxemia prompted evaluation for central hypoventilation, confirmed by means of transcutaneous capnography and nocturnal pulse oximetry. Genetic testing revealed a de novo nonsense mutation in exon 1 of PHOX2B (p.Tyr14Ter). Brain magnetic resonance imaging showed diffuse white matter changes suggestive of gliosis. Further investigations identified early-onset systemic hypertension, requiring antihypertensive therapy. The patient was discharged on nocturnal non-invasive ventilation and enrolled in a neurodevelopmental rehabilitation program. Conclusions: This case highlights the phenotypic variability of CCHS and the importance of considering this diagnosis in children presenting with unexplained hypercapnia and sleep-related hypoxemia. It underscores the need for comprehensive autonomic evaluation, including blood pressure monitoring. The p.Tyr14Ter variant may allow partial protein function, potentially accounting for the relatively mild phenotype.

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