Small nerve fibres, small hands and small feet: a new syndrome of pain, dysautonomia and acromesomelia in a kindred with a novel NaV1.7 mutation.

摘要: The NaV1.7 sodium channel is preferentially expressed within dorsal root ganglion and sympathetic neurons their small-diameter peripheral axons. Gain-of-function variants of have recently been described in patients with painful small fibre neuropathy no other apparent cause. Here, we describe a novel syndrome pain, dysautonomia, hands feet kindred carrying mutation. A 35-year-old male presented erythema burning pain the since early childhood, later disseminating to feet, cheeks ears. He also experienced progressive muscle cramps, profound sweating, bowel disturbances (diarrhoea or constipation), episodic dry eyes mouth, hot flashes, erectile dysfunction. Neurological examination was normal. Physical remarkable revealing (acromesomelia). Blood nerve conduction studies were unremarkable. Intra-epidermal density significantly reduced compared age- sex-matched normative values. patient's brother father reported similar complaints including distal extremity redness demonstrated comparable limb under-development. Quantitative sensory testing revealed impaired warmth sensation proband, brother. Genetic analysis missense mutation SCN9A gene encoding (G856D; c.2567G > A) all three affected subjects, but not unaffected family members. Functional that hyperpolarizes (−9.3 mV) activation, depolarizes (+6.2 mV) steady-state fast-inactivation, slows deactivation enhances persistent current response slow ramp stimuli by 10- 11-fold wild-type channels. Current-clamp transfected G856D mutant channels depolarized resting potential, threshold, increased repetitive firing suprathreshold stimulation spontaneous firing. Our results demonstrate produces DRG neuron hyperexcitability which underlies this kindred, suggest dysfunction due may contributed under-development syndrome. * Abbreviations : DRG