ORPHA: 306577; DO: 0111730;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 3p22.2 | Episodic pain syndrome, familial, 2 | 615551 | Autosomal dominant | 3 | SCN10A | 604427 |
A number sign (#) is used with this entry because of evidence that familial episodic pain syndrome-2 (FEPS2) is caused by heterozygous mutation in the SCN10A gene (604427) on chromosome 3p22.
Familial episodic pain syndrome-2 is an autosomal dominant neurologic disorder characterized by adult-onset of paroxysmal pain mainly affecting the distal lower extremities (summary by Faber et al., 2012).
For a discussion of genetic heterogeneity of familial episodic pain syndrome, see 615040.
Faber et al. (2012) reported a man who developed burning and intense paroxysmal itch in the feet at age 57 years. Nerve conduction studies were normal, but skin biopsy showed reduced intraepidermal nerve fiber density in the distal leg. His son developed a similar disorder with allodynia and hyperalgesia at age 39 years; he also had well-controlled type 1 diabetes mellitus. Skin biopsy showed complete epidermal denervation. Nerve conduction velocity studies showed decreased action potential amplitudes, suggesting involvement of larger fibers. An unrelated woman developed stabbing pain in her feet, lower legs, and hands at age 65 years. Warmth gave some relief, and her soles occasionally showed red discoloration. Nerve conduction studies were normal, but quantitative sensory testing showed abnormal thresholds for warmth and cold sensation in both feet. Skin biopsy showed normal intraepidermal nerve fiber density.
The transmission pattern of FEPS2 in the family reported by Faber et al. (2012) was consistent with autosomal dominant inheritance.
In a father and son with adult-onset FEPS2, Faber et al. (2012) identified a heterozygous missense mutation in the SCN10A gene (L554P; 604427.0001). An unrelated woman with a similar disorder carried a different heterozygous mutation in SCN10A (A1304T; 604427.0002). In vitro functional expression studies in mouse dorsal root ganglia neurons showed that both mutations caused enhanced channel electrical activities and induced hyperexcitability of dorsal root ganglia neurons. The findings indicated that gain-of-function mutations in SCN10A can cause an episodic pain disorder.
Faber, C. G., Lauria, G., Merkies, I. S. J., Cheng, X., Han, C., Ahn, H.-S., Persson, A.-K., Hoeijmakers, J. G. J., Gerrits, M. M., Pierro, T., Lombardi, R., Kapetis, D., Dib-Hajj, S. D., Waxman, S. G. Gain-of-function Nav1.8 mutations in painful neuropathy. Proc. Nat. Acad. Sci. 109: 19444-19449, 2012. [PubMed: 23115331] [Full Text: https://doi.org/10.1073/pnas.1216080109]