A Multidisciplinary Approach to Navigating Variants of Uncertain Significance in Sudden Infant Deaths

Abstract

The sudden death of a previously healthy infant is a devastating event for a family—the death of 2 even more unimaginable. Prior to the debunking of Meadow's law, a legal concept attributing multiple unexplained infant deaths to Munchausen by proxy, these events could lead to the wrongful prosecution of those who had lost their children to “sudden unexpected infant death (SUID).” Today, these cases, wherein multiple infants within one family pass inexplicably, raise suspicion for a possible genetic cause and point toward a need for postmortem genetic testing.

We present the case of 2 siblings who passed suddenly in infancy, with no structural cause of death identified at autopsy. Genetic testing in both infants found the same variant of uncertain significance, a heterozygous single nucleotide substitution, denoted c.3191C>T, in SCN10A, which encodes a sodium channel with pathogenic variants possibly implicated in sudden cardiac death syndromes. Although it is unclear at this time if the variant of uncertain significance identified was a contributing factor in the deaths, the case emphasized the importance of involving a multidisciplinary team to ensure appropriate pretest and posttest counseling, interpretation of nuanced testing results, and medical follow-up for surviving family members of SUID.