De novo gain-of-function mutation in SCN11A: No pain, More pain, or a bit of Both?

Background: The genotypic and phenotypic spectrum of pain-related channelopathies is expanding. Various mutations in the genes encoding voltage-gated sodium channels have been identified. This is best exemplified in SCN9A gene mutations whereby loss-of-function mutations lead to indifference to pain. 1,2 Conversely, gain-of-function mutations result in paroxysmal extreme pain disorder and primary erythermalgia. 3 Recently, Leipold et al. (2013) reported 2 cases of congenital insensitivety to pain due to a de novo gain-of-function mutation in SCN11A.4 Clinically, patients had universal loss of pain perception and self-inflicted injuries. Aim: To describe a case with a similar SCN11A mutation in whom a mixed picture of pain insensitivity and episodic visceral pain predominates. Case report: This 6-year-old girl had a history of chronic diarrhoea and failure to thrive during the first year of life. Difficult-to-heal wounds were noted. Moreover, she had mouth ulcers that were self-inflicted by biting. Cognitive development was normal. Motor development was slightly delayed with generalized hypotonia and weakness. She then started to have abdominal pain made worse by defecation and urination.  Other symptoms were excessive sweating, persistent pruritus and cold intolerance. A de novo heterozygous mutation in SCN11A which encodes one of the sodium channels (Na v 1.9) was found. This was a p.Leu811Pro missense gain-of-function mutation. Discussion & Conclusion: This case expands the phenotype of a novel mutation in a gene encoding a voltage-gated sodium channel. Mutational analysis of SCN11A gene in similar cases is recommended. Studies to increase understanding of pain pathways and targeted treatments are needed.