Congenital central hypoventilation syndrome: clinical features, molecular genetic basis, DNA diagnostics

Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder, characterized by primary alveolar hypoventilation and autonomic dysregulation. CCHS is caused in 92% of patients by heterozygous polyalanine expansion from 24 to 33 repeats, located in exon 3 of PHOX2B gene. Missense, nonsense and frameshift PHOX2B mutations explain most of the remaining cases. There is a correlation between the mutation type and the severity of the phenotype in CCHS. Mutations occur de novo in 90-95% of cases. Alleles with 24-25 repeats are classified as incomplete penetrance alleles. These alleles are the cause of congenital central hypoventilation syndrome with late-onset and may explain the re-birth of sick children from asymptomatic parents in some cases. This article shows basic information on central congenital hypoventilation syndrome and the results of molecular diagnostics CCHS in FSBI «RCMG».