Autosomal recessive congenital indifference to pain can be caused by loss-of-function mutations in the SCN9A gene encoding a voltage-gated sodium channel. Gain-of-function mutations in the same gene cause autosomal dominant primary erythermalgia. Although indifference and insensitivity are considered distinct, with pathological changes in peripheral nerves a feature of insensitivity, the absence of the ion channel is not morphologically obvious and the indifference is likely to be because of the absence of the sensation of pain. An autosomal dominant form has also been reported. Congenital insensitivity to pain with anhidrosis (CIPA) is caused by defects in the neurotrophic tyrosine kinase-1 receptor (a nerve growth factor receptor).
Subjects: Medicine and Health.