Novel mutation of SCN9A gene in a family with Paroxysmal Extreme Pain Disorder (PEPD): Considerations of paediatric interest

Paroxysmal Extreme Pain Disorder (PEPD) – previously known as Familial Rectal Pain Syndrome [1] – is a rare autosomal dominant disease with fewer than 500 patients documented [2].
PEPD is caused by mutations in the SCN9A gene, which encodes the NaV1.7 voltage-gated sodium channel α-subunit [1]. The NaV1.7 is especially expressed in nociceptive neurons at the dorsal root ganglion and sympathetic ganglia neurons [2,3], but it is also present in the nerves innervating arterioles and arterio-venous shunts in the glabrous skin, the vascular myocytes and the vascular endothelium in human skin [1]. SCN9A mutations are causally associated with two phenotypic presentations: painful conditions (inherited erythromelalgia, small-fibre neuropathy and PEPD) and loss-of- pain-sensation conditions (congenital insensitivity to pain) [1,4].
PEPD-related NaV1.7 mutations impair channel inactivation and prolong action potentials and repetitive nociceptor firing in the areas where it is expressed, in response to provoking stimuli, which produces a hyperexcitable and persistently activated sodium channel, increasing the excitability of sensory neurons [4,5].
Symptoms generally begin in early infancy with episodes of excruciating,burning and spreading pain in the lower part of the body, typically in the anorectal area, which can last from seconds to hours [2,5]. This pain is oftenaccompanied byerythema(harlequin colour change) [6]. PEPD is usually triggered by mechanical stimuli [1]. Pain episodes can also affect the ocular and mandibular regions

Author(s): Jerez Calero Antonio

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