Abstract
We describe a case of familial episodic pain syndrome with autosomal dominant inheritance that is caused by a gain-of-function mutation (Arg225Cys) in the SCN11A gene. In contrast to the phenotype of small fiber sensory neuropathy with mutations in voltage-gated sodium channels, our patient and her affected family members present with deep aching, mimicking fibromyalgia. In line with the feature of pain, patients respond well to non-steroidal anti-inflammatory drugs. Moreover, there is no detectable large or small nerve fiber degeneration. Together, these characteristics make the familial episodic pain syndrome clearly distinctive from small fiber sensory neuropathy.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Waxman SG. Channelopathic pain: a growing but still small list of model disorders. Neuron. 2010;66(5):622–4.
Kremeyer B, Lopera F, Cox JJ, Momin A, Rugiero F, Marsh S, et al. A gain-of-function mutation in TRPA1 causes familial episodic pain syndrome. Neuron. 2010;66(5):671–80.
Hoeijmakers JG, Faber CG, Merkies IS, Waxman SG. Painful peripheral neuropathy and sodium channel mutations. Neurosci Lett. 2015;596:51–9.
Dib-Hajj SD, Tyrrell L, Black JA, Waxman SG. NaN, a novel voltage-gated Na channel, is expressed preferentially in peripheral sensory neurons and down-regulated after axotomy. Proc Natl Acad Sci U S A. 1998;95(15):8963–8.
Persson AK, Black JA, Gasser A, Cheng X, Fischer TZ, Waxman SG. Sodium-calcium exchanger and multiple sodium channel isoforms in intra-epidermal nerve terminals. Mol Pain. 2010;6:84.
Zhao P, Barr TP, Hou Q, Dib-Hajj SD, Black JA, Albrecht PJ, et al. Voltage-gated sodium channel expression in rat and human epidermal keratinocytes: evidence for a role in pain. Pain. 2008;139(1):90–105.
Fang X, Djouhri L, Black JA, Dib-Hajj SD, Waxman SG, Lawson SN. The presence and role of the tetrodotoxin-resistant sodium channel Na(v)1.9 (NaN) in nociceptive primary afferent neurons. J Neurosci. 2002;22(17):7425–33.
Yang Y, Wang Y, Li S, Xu Z, Li H, Ma L, et al. Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia. J Med Genet. 2004;41(3):171–4.
Fertleman CR, Baker MD, Parker KA, Moffatt S, Elmslie FV, Abrahamsen B, et al. SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes. Neuron. 2006;52(5):767–74.
Fertleman CR, Ferrie CD, Aicardi J, Bednarek NA, Eeg-Olofsson O, Elmslie FV, et al. Paroxysmal extreme pain disorder (previously familial rectal pain syndrome). Neurology. 2007;69(6):586–95.
Faber CG, Hoeijmakers JG, Ahn HS, Cheng X, Han C, Choi JS, et al. Gain of function Nanu1.7 mutations in idiopathic small fiber neuropathy. Ann Neurol. 2012;71(1):26–39.
Cox JJ, Reimann F, Nicholas AK, Thornton G, Roberts E, Springell K, et al. An SCN9A channelopathy causes congenital inability to experience pain. Nature. 2006;444(7121):894–8.
Faber CG, Lauria G, Merkies IS, Cheng X, Han C, Ahn HS, et al. Gain-of-function Nav1.8 mutations in painful neuropathy. Proc Natl Acad Sci U S A. 2012;109(47):19444–9.
Huang J, Han C, Estacion M, Vasylyev D, Hoeijmakers JG, Gerrits MM, et al. Gain-of-function mutations in sodium channel Na(v)1.9 in painful neuropathy. Brain. 2014;137(Pt 6):1627–42.
Han C, Yang Y, Te Morsche RH, Drenth JP, Politei JM, Waxman SG, et al. Familial gain-of-function Nav1.9 mutation in a painful channelopathy. J Neurol Neurosurg Psychiatry. 2017;88(3):233–40.
Okuda H, Noguchi A, Kobayashi H, Kondo D, Harada KH, Youssefian S, et al. Infantile pain episodes associated with Novel Nav1.9 mutations in familial episodic pain syndrome in Japanese Families. PLoS One. 2016;11(5):e0154827.
Zhang XY, Wen J, Yang W, Wang C, Gao L, Zheng LH, et al. Gain-of-function mutations in SCN11A cause familial episodic pain. Am J Hum Genet. 2013;93(5):957–66.
Castoro R, Simmons M, Ravi V, Huang D, Lee C, Sergent J, et al. SCN11A Arg225Cys mutation causes nociceptive pain without detectable peripheral nerve pathology. Neurol Genet. 2018;4(4):e255.
Leipold E, Liebmann L, Korenke GC, Heinrich T, Giesselmann S, Baets J, et al. A de novo gain-of-function mutation in SCN11A causes loss of pain perception. Nat Genet. 2013;45(11):1399–404.
Rolyan H, Liu S, Hoeijmakers JG, Faber CG, Merkies IS, Lauria G, et al. A painful neuropathy-associated Nav1.7 mutant leads to time-dependent degeneration of small-diameter axons associated with intracellular Ca2+ dysregulation and decrease in ATP levels. Mol Pain. 2016;12:174480691667447.
de Greef BT, Merkies IS, Geerts M, Faber CG, Hoeijmakers JG. Efficacy, safety, and tolerability of lacosamide in patients with gain-of-function Nav1.7 mutation-related small fiber neuropathy: study protocol of a randomized controlled trial-the LENSS study. Trials. 2016;17(1):306.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Castoro, R., Li, J., Zhou, L. (2020). A 39-Year-Old Woman with Intermittent Bilateral Foot and Leg Pain since Childhood. In: Zhou, L., Burns, D., Cai, C. (eds) A Case-Based Guide to Neuromuscular Pathology. Springer, Cham. https://doi.org/10.1007/978-3-030-25682-1_41
Download citation
DOI: https://doi.org/10.1007/978-3-030-25682-1_41
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-25681-4
Online ISBN: 978-3-030-25682-1
eBook Packages: MedicineMedicine (R0)