Abstract Details

Title Arg225Cys Mutation in SCN11A Causes Nociceptive Pain without Detectable Peripheral Nerve Pathology

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S42 - Neuromuscular Disorders (4:25 PM-4:36 PM)

Poster/Presentation
Number 006

Background Mutations affecting the alpha-subunits of voltage-gated sodium channels (SCN9A,SCN10A and SCN11A) in small fiber and small diameter peripheral DRG neurons have been shown to cause inherited pain disorders. The SCN11A Arg225Cys mutation has been described in literature as causing an episodic pain syndrome(EPS). However, the EPS was not systematically characterized; in particular, it is unknown whether these patients are associated with pathological or electrophysiological changes of peripheral neuropathy

Objective The SCN11A gene encodes the Na_V1.9 sodium channel found exclusively in peripheral nociceptive neurons. However, mutations in SCN11A have been linked to multiple clinical phenotypes, including familial episodic pain syndrome, sporadic small fiber sensory neuropathy and congenital inability to experience pain. We have identified a family with an Arg225Cys missense mutation in SCN11A gene. This study is to systematically characterize genotype, clinical and pathophysiological phenotypes in the family.

Design/Methods

All enrolled subjects were evaluated clinically, by electrophysiological studies, DNA sequencing and punch skin biopsies.

Results

All affected family members are afflicted by episodes of pain. The pain was predominantly nociceptive, but not neuropathic in nature, which led a diagnosis of fibromyagia in some patients. All patients had normal findings in nerve conduction studies for detecting large nerve fiber neuropathies and skin biopsies for detecting small nerve fiber pathology.

Conclusions

Unlike those patients with missense mutations in SCN11A, small fiber sensory neuropathy and neuropathic pain, the Arg225Cys SCN11A in the present study causes nociceptive pain without neuropathic pain and any detectable pathophysiological changes of peripheral neuropathy. This finding is consistent with dysfunction of nociceptive neurons. In addition, since the nociceptive pain in patients has led to the diagnosis of fibromyalgia, this justifies a future search of mutations of SCN11A in patients with additional pain phenotypes such as fibromyalgia to expand clinical spectrum beyond painful small fiber sensory neuropathy.

Authors/Disclosures
Ryan Castoro, DO (Vanderbilt University Medical Center) PRESENTER	No disclosure on file
Jun Li, MD, PhD, FAAN (Harris Methodist Hospital)	The institution of Dr. Li has received personal compensation in the range of $500-$4,999 for serving as a Consultant for FDA. The institution of Dr. Li has received research support from NIH. Dr. Li has a non-compensated relationship as a Associate Editor of ACTN journal with ANA that is relevant to AAN interests or activities.
Christopher D. Lee, MD (Vanderbilt University Medical Center)	Dr. Lee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx.
Lan Zhou, MD, PhD (Hospital for Special Surgery Department of Neurology)	The institution of Dr. Zhou has received research support from NIH.

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