Severe Positional Central Sleep Apnea in an Asymptomatic Adult With a PHOX2B Frameshift Mutation

Area of Science:

• Genetics
• Sleep Medicine
• Pediatrics

Background:

• Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder.
• PHOX2B gene mutations are the primary cause of CCHS.
• CCHS typically presents in infancy with hypoventilation and autonomic dysfunction.

Observation:

• An adult patient with a PHOX2B frameshift mutation was diagnosed with CCHS.
• The mutation was identified after his daughter presented with hypoventilation and neuroblastoma.
• The patient initially had no symptoms but polysomnography revealed severe positional hypercapnic central sleep apnea.

Findings:

• The patient's sleep apnea was partially responsive to positional therapy.
• Noninvasive ventilation resolved central breathing events and improved sleep quality.
• This case highlights variable expressivity of PHOX2B mutations.

Implications:

• Clinicians must recognize the diverse presentations of CCHS in adults.
• Awareness of PHOX2B mutation variability is crucial for timely diagnosis.
• Early intervention can prevent severe cardiorespiratory and neurocognitive issues in affected individuals.