A new nonsense pathogenic variant in exon 1 of PHOX2B leads to the diagnosis of congenital central hypoventilation syndrome with intra-familial variability.

Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder of the autonomic nervous system resulting in decreased brain sensitivity to hypercapnia and hypoxia characterized by a genetic abnormality in the pair-like homeobox 2B (PHOX2B) gene. Most patients have a heterozygous expansion of the polyalanine repeat in exon 3 (PARM), while 10 % of patients have non-PARM (NPARM) mutations that can span the entire gene. The majority of pathogenic variants are de novo, but variants with incomplete penetrance can be identified in the heterozygous state.