PHOX2B mutation-confirmed congenital central hypoventilation syndrome in a Chinese family: presentation from newborn to adulthood.

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is characterized by compromised chemoreflexes resulting in sleep hypoventilation. We report a Chinese family with paired-like homeobox 2B (PHOX2B) mutation-confirmed CCHS, with a clinical spectrum from newborn to adulthood, to increase awareness of its various manifestations.

METHODS: After identifying central hypoventilation in an adult man (index case), clinical evaluation was performed on the complete family, which consisted of the parents, five siblings, and five offspring. Pulmonary function tests, overnight polysomnography, arterial blood gas measurements, hypercapnia ventilatory response, and PHOX2B gene mutation screening were performed on living family members. Brain MRI, 24-h Holter monitoring, and echocardiography were performed on members with clinically diagnosed central hypoventilation.

RESULTS: The index patient and four offspring manifested clinical features of central hypoventilation. The index patients had hypoxia and hypercapnia while awake, polycythemia, and hematocrit levels of 70%. The first and fourth children had frequent cyanotic spells, and both died of respiratory failure. The second and third children remained asymptomatic until adulthood, when they experienced impaired hypercapnic ventilatory response. The third child had nocturnal hypoventilation with nadir pulse oximetric saturation of 59%. Adult-onset CCHS with PHOX2B gene mutation of the + 5 alanine expansions were confirmed in the index patient and the second and third children. The index patient and the third child received ventilator support system bilevel positive airway pressure treatment, which improved the hypoxemia, hypercapnia, and polycythemia without altering their chemosensitivity.

CONCLUSIONS: Transmission of late-onset CCHS is autosomal-dominant. Genetic screening of family members of CCHS probands allows for early diagnosis and treatment.