Medico-legal investigation in an explicable case of congenital central hypoventilation syndrome due to a rare variant of the PHOX2B gene

The heterozygous PHOX2B gene mutation is related to congenital central hypoventilation syndrome (CCHS). It is characterized by defective autonomous nervous system development leading to inadequate breathing response to hypoxia and hypercapnia, leading to hypoventilation especially during non-REM sleep, but also during waking in the more severe cases. Herein we report a case of sudden death in a 28-day-old child. The mother reported the infant was found lying on her own bed in the prone position. The infant was wearing a romper and lying in her crib without any blanket or other objects. At autopsy no significant pathological findings were detected. Histologically, sparse aspirated milk residues were present in some lung fields. Toxicological and microbiological examinations were within the norm. The initial postmortem investigation ruled out any readily identifiable cause of death. However, genetic analysis revealed a rare heterozygous 21bp in-frame deletion of the polyalanine coding sequences of the PHOX2B gene. In-frame contractions of the poly-Ala tract of the PHOX2B gene have already been reported in patients with symptoms suggestive of sporadic hypoventilation, apparent life-threatening events or neonatal respiratory distress