The phenotype of congenital insensitivity to pain due to the NaV1. 9 variant p. L811P

CG Woods, MOE Babiker, I Horrocks… - European Journal of …, 2015 - nature.com
CG Woods, MOE Babiker, I Horrocks, J Tolmie, I Kurth
European Journal of Human Genetics, 2015nature.com
Individuals with congenital insensitivity to pain (CIP) have never felt pain despite possessing
an anatomically normal peripheral nervous system and normal intelligence. 1 In 2006/7,
biallelic null mutations in the transmembrane voltage-gated sodium channel NaV1.
7/SCN9A were discovered as a cause of CIP. 2, 3 Recently, a new form of CIP was reported
in two isolated unrelated cases. Both had recurrent injuries and self-mutilations secondary to
feeling no pain, and identical de novo heterozygous p. L811P variants in the voltage-gated …
Individuals with congenital insensitivity to pain (CIP) have never felt pain despite possessing an anatomically normal peripheral nervous system and normal intelligence. 1 In 2006/7, biallelic null mutations in the transmembrane voltage-gated sodium channel NaV1. 7/SCN9A were discovered as a cause of CIP. 2, 3 Recently, a new form of CIP was reported in two isolated unrelated cases. Both had recurrent injuries and self-mutilations secondary to feeling no pain, and identical de novo heterozygous p. L811P variants in the voltage-gated sodium channel NaV1. 9, encoded by SCN11A. 4 We have now identified a further case with the identical variant c. 2432T> C (p.(L811P)) and report that all have a complex extended phenotype, see Table 1. The presenting feature in all three was failure to thrive secondary to intestinal dysmotility. Consequent upon this, all had multiple hospital admissions and investigations and two required parenteral nutrition. Abnormal gut peristalsis was found; however, intestinal biopsies were repeatedly normal. All have continuing problems with diarrhoea and/or constipation.
All three have severe pruritus, scratching themselves sufficiently to cause full-thickness skin loss in the cervical area during infancy (see Figure 1). Remarkably this was at the same location as seen in transgenic Scn11a-mutant mice. 4 Ulceration and itching may be secondary to hyperhidrosis, as itching only reduced following the use of cyprohepatidine, which lead to a clear reduction in sweating. Hyperhidrosis persisted throughout life, and increased on exertion and raised ambient temperatures. All cried and blushed normally, and none had any abnormal cardiovascular findings nor emotional liability.
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