Pain experience of children with Christianson syndrome.

Abstract

Children with Christianson syndrome (CS), an X-linked neurodevelopmental disorder caused by loss-of-function mutations in the alkali cation/proton exchanger SLC9A6/NHE6, display severe cognitive impairments, mutism, and sensory abnormalities such as hyposensitivity to pain. However, it is unclear whether these children display other sensory abnormalities and whether their pain hyposensitivity is the result of an elevated pain threshold or a complete insensitivity to pain. To better characterize the sensory abnormalities in this disorder, we used a combination of a mouse model of CS and pain questionnaires directed at nonverbal patients with CS. We recruited 14 young male participants with CS and subjected them to a novel observational tool, the Pain Sensory and Painful Situations Questionnaire (PSQ), which takes multiple painful situations into account to broaden the description of pain expression. By analyzing social expressive behaviours of pain in these nonverbal patients, the PSQ documented that over 60% of the participants were unaffected by mechanical or inflammatory painful stimuli. This reduced pain sensitivity was also observed in the mouse CS model. Surprisingly, CS mice also displayed aversive reactions to innocuous stimuli, which prompted us to examine whether such reactions were also present in children with CS. Indeed, the results from the PSQ revealed that 30% to 50% of these patients showed an aversive response to normally innocuous stimuli like light touch and gusts of air. Our results demonstrate that children with CS have aversive reactions to innocuous stimuli and are hyposensitive to painful stimuli, the latter making them at risk for developing complications from unreported injuries.