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 ... 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 ... 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.
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 (A1304T; 604427.0002). In ... 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 (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 hyperexcitablity of dorsal root ganglia neurons. The findings indicated that gain-of-function mutations in SCN10A can cause an episodic pain disorder.