Congenital central hypoventilation syndrome: a report of four cases

Abstract

Objective To study the molecular genetic mechanism of congenital central hypoventilation syndrome (CCHS). Method The clinical data and molecular genetics results of CCHS diagnosed in neonatology department from 2014 to 2016 were analyzed retrospectively. The relationship between genotypes and clinical phenotypes in patients of CCHS was analyzed, and the diagnostic thinkings, follow-up and prognosis were summarized. Result A total of 4 infants with CCHS were included in this study. Among them, 2 were boys and the other 2 were girls. They were all full-term neonates without asphyxia at birth, but they soon sufferd from dyspnea and cyanosis, required assisted ventilation. One case had difficult defecation. All 4 cases had difficulty in weaning. The respiratory rhythm became weak developed apnea and carbon dioxide retention was detected in blood gas analysis. All the 4 cases died after withdrawal of treatment. The results of molecular genetic testing were as follows. There was a 38bp heterozygous deletion mutation in exon 3 of gene PHOX2B (e.756_776 del21bp). Three cases were found small fragment insertion in exon 3 of gene PHOX2B, which attributed to polyalanine repeat expansion mutations (PARMs). One case belonged to type 20/27 and another 2 cases belonged to type 20/26. Conclusion The main manifestation of CCHS in the neonatal period is ventilator dependant, which can combined with megacolon and atypical autonomic nerve disorder. According to the literature, more than 95% of CCHS are caused by the PHOX2B mutation. The symptom is severe when it got a non-PARMs mutation. It′s useful to make a definite diagnosis with genetic diagnosis results, which could be helpful for treating and predicting. Only effective respiratory support and standardized follow-up system can improve the quality of life in patients of CCHS. Key words: Sleep apnea, central; Hypoventilation; Genetic association studies; Congenital central hypoventilation syndrome