PHOX2B Mutation-Confirmed Congenital Central Hypoventilation Syndrome in a Chinese Family.

Center of Sleep Disorder, National Taiwan University Hospital, Taipei, Taiwan.

Background Congenital central hypoventilation syndrome (CCHS) is characterized by compromised chemo-reflexes resulting in sleep hypoventilation. We report a Chinese family with PHOX2B mutation-confirmed CCHS, with a clinical spectrum from newborn to adulthood, to increase awareness on its various manifestations. Methods After identifying central hypoventilation in an adult male (index case), clinical evaluation was performed on the complete family, which consisted of the parents, five siblings, and five offsprings. Pulmonary function tests, overnight polysomnography, arterial blood gases, hypercapnia ventilatory response, and PHOX2B gene mutation screening were performed on living family members. Brain MRI, 24-h Holter, and echocardiography were done on members with clinically diagnosed central hypoventilation. Results The index patient and four offsprings manifested with clinical features of central hypoventilation. The index patients had hypoxia and hypercapnia while awake, polycythemia, and hematocrit 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 SpO(2) 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 BiPAP treatment, which improved the hypoxemia, hypercapnia, and polycythemia without altering their chemo-sensitivity. Conclusions Transmission of late-onset CCHS is autosomal-dominant. Genetic screening of family members of CCHS probands allows for early diagnosis and treatment.

PMID: 18849397 [PubMed - as supplied by publisher]