PHOX2B mutations in three Chinese patients with congenital central hypoventilation syndrome

• Published in: Chinese medical journal 2006-10, Vol.119 (20), p.1749-1752
• Main Authors: Or, Siu-Fong June, Tong, Ming-for Tony, Lo, Fai-Man Ivan, Law, Chi-Wai, Miu, Ting-Yat, Trochet, Delphine, Lam, Tak-Sum Stephen
• Format: Article
• Language: English
• Subjects: Homeodomain Proteins - genetics; Humans; Infant, Newborn; Male; Mutation; Promoter Regions, Genetic; Sleep Apnea, Central - congenital; Sleep Apnea, Central - genetics; Syndrome; Transcription Factors - genetics; 病理机制; 肺疾病; 肺通气
• ISSN: 0366-6999; 2542-5641
• DOI: 10.1097/00029330-200610020-00014

Congenital central hypoventilation syndrome （CCHS, OMIM #209880） is a rare autosomal dominant disorder of the autonomic nervous system （ANS） characterized by an abnormal autonomic ventilatory response to progressive hypercarbia and sustained hypoxemia. Patients typically present in the newborn period with hypoventilation or apnea asleep, awake, or both, without any associated cardiac, pulmonary, neuromuscular or brainstem lesions. Rarely, some patients may present at a later age and are diagnosed to have late onset central hypoventilation syndrome （LOCHS）.1 Other features of ANS dysfunction such as feeding difficulty due to oesophageal dysmotility, severe constipation in the absence of Hirschsprung disease, poor regulation of basal body temperature, episodes of profuse sweating, pupillary and ocular abnormalities, decreased beat-to-beat variability of heart rate, attenuated response of heart rate to exercise, abnormal fluctuation of blood pressure, decreased perception to pain, and decreased perception to anxiety may be variably present but not essential for diagnosis Furthermore, this central hypoventilation can occur as an isolated feature or in association with a number of neurocristopathies, notably Hirschsprung disease （Haddad syndrome, OMIM #209880） and tumours of the sympathetic nervous system particularly neuroblastoma, ganglioneuro- blastoma, and ganglioneuroma, which were found in 20% and 5%--10% of CCHS patients, respectively.2 Studies of genes pertinent to the early embryologic development of the neural crest cells, specifically the endothelin and the RET-GDNF signaling pathways, have recently led to the identification of PHOX2B as the major disease causing gene for CCHS.2-6 PHOX2B was mapped to chromosome 4p12 and consists of 3 exons. It encodes a highly conserved paired-like homeobox transcription factor of 314 amino acids linked to the RET-GDNF signaling