Leipold et al. (2013) reported 2 unrelated patients, a German girl and a Swedish boy, with hereditary sensory and autonomic neuropathy. The clinical history of both affected individuals was remarkably similar, involving a congenital inability to experience pain ... Leipold et al. (2013) reported 2 unrelated patients, a German girl and a Swedish boy, with hereditary sensory and autonomic neuropathy. The clinical history of both affected individuals was remarkably similar, involving a congenital inability to experience pain since birth resulting in self-mutilations, slow-healing wounds, and multiple painless fractures. Both patients also had mild muscle weakness and delayed motor development. Muscle biopsy and electromyography (EMG) were normal. Electroneurography showed slightly reduced motor and sensory nerve conduction velocities with normal amplitudes. Sural nerve biopsy of 1 patient did not show sensory axonal loss, and brain MRI and cognitive function were normal. Both patients also had hyperhidrosis and gastrointestinal dysfunction necessitating temporary parenteral nutrition, suggesting autonomic involvement. Intestinal biopsies from both patients were normal.
In 2 unrelated patients with HSAN7, Leipold et al. (2013) identified the same de novo heterozygous missense mutation in the SCN11A gene (L811P; 604385.0001). The mutation in the first patient was found by whole-exome sequencing. The second mutation ... In 2 unrelated patients with HSAN7, Leipold et al. (2013) identified the same de novo heterozygous missense mutation in the SCN11A gene (L811P; 604385.0001). The mutation in the first patient was found by whole-exome sequencing. The second mutation was found by sequencing of the SCN11A gene in 58 individuals with early-onset severe sensory loss. Transfection of the mutation into mice resulted in reduced pain sensitivity. Electrophysiologic studies in dorsal root ganglia from mutant mice and in isolated cells showed that the mutation resulted in a gain of function with a left-shift in resting membrane potential and channel activation and a decrease in the kinetics of channel deactivation. Leipold et al. (2013) hypothesized that this excess sodium influx and subsequent cell depolarization at rest may cause progressive conduction block in other ion channels that form the main constituents of the action potential in dorsal root ganglia neurons. Insufficient activation of calcium ion channels would result in impaired neurotransmitter release at presynaptic nerve terminals to transmit pain signals to the spinal cord.